T cell-mediated host immune defenses in the lung

Annual Review of Immunology

Volumn 31, Issue , 2013, Pages 605-633

  Chen, Kong ^a   Kolls, Jay K ^a  

^a CHILDREN S HOSPITAL OF PITTSBURGH   (United States)

Author keywords

Coinfection; Inflammation; Pneumonia

Indexed keywords

AZITHROMYCIN; CIPROFLOXACIN; ETHAMBUTOL; GAMMA INTERFERON; INTERLEUKIN 12; INTERLEUKIN 13; INTERLEUKIN 17; INTERLEUKIN 4; RECOMBINANT GAMMA INTERFERON; RECOMBINANT INTERLEUKIN 12; RIFAMPICIN; STAT3 PROTEIN; STAT4 PROTEIN; STAT6 PROTEIN; TRANSCRIPTION FACTOR GATA 3; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA;

ADAPTIVE IMMUNITY; ADOPTIVE TRANSFER; ANTIGEN PRESENTING CELL; ANTIVIRAL ACTIVITY; BACTERIAL CLEARANCE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL INFILTRATION; CELL LINEAGE; CELLULAR IMMUNITY; CHRONIC OBSTRUCTIVE LUNG DISEASE; COCCIDIOIDOMYCOSIS; CYSTIC FIBROSIS; CYTOKINE PRODUCTION; CYTOKINE RELEASE; HAEMOPHILUS INFLUENZAE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HOST RESISTANCE; HUMAN; HUMORAL IMMUNITY; INNATE IMMUNITY; LUNG INFECTION; LYMPHOID CELL; MIXED INFECTION; MUCOSAL IMMUNITY; MYCOBACTERIOSIS; MYCOPLASMA PNEUMONIA; NATURAL KILLER T CELL; NONHUMAN; PNEUMOCYSTOSIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; RESPIRATORY SYNCYTIAL PNEUMOVIRUS; REVIEW; STAPHYLOCOCCUS AUREUS; STREPTOCOCCUS PNEUMONIAE; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TH1 CELL; TH17 CELL; TH2 CELL; TULAREMIA; VIRAL CLEARANCE; VIRUS LOAD;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; HOST-PATHOGEN INTERACTIONS; HUMANS; LUNG; LYMPH NODES; MYCOBACTERIUM TUBERCULOSIS; TUBERCULOSIS, PULMONARY;

EID: 84875516365     PISSN: 07320582     EISSN: 15453278     Source Type: Book Series    
DOI: 10.1146/annurev-immunol-032712-100019     Document Type: Review

References (193)

1. Marshall NB, Swain SL. 2011. Cytotoxic CD4 T cells in antiviral immunity. J. Biomed. Biotechnol. 2011:954602
2. GeurtsvanKessel CH, Lambrecht BN. 2008. Division of labor between dendritic cell subsets of the lung. Mucosal Immunol. 1(6):442-50
3. Shafiani S, Tucker-Heard G, Kariyone A, Takatsu K, Urdahl KB. 2010. Pathogen-specific regulatory Tcells delay the arrival of effectorTcells in the lung during early tuberculosis. J. Exp.Med. 207(7):1409-20
4. Le Goffic R, Arshad MI, Rauch M, L'Helgoualc'h A, Delmas B, et al. 2011. Infection with influenza virus induces IL-33 in murine lungs. Am. J. Respir. Cell Mol. Biol. 45(6):1125-32
5. Lund FE, Partida-Sanchez S, Lee BO, Kusser KL, Hartson L, et al. 2002. Lymphotoxin-deficient mice make delayed, but effective, T and B cell responses to influenza. J. Immunol. 169(9):5236-43
6. Olmos S, Stukes S, Ernst JD. 2010. Ectopic activation of Mycobacterium tuberculosis-specific CD4+ T cells in lungs of CCR7-/-mice. J. Immunol. 184(2):895-901
7. Altare F, Lammas D, Revy P, Jouanguy E, Doffinger R, et al. 1998. Inherited interleukin 12 deficiency in a child with bacille Calmette- Guérin and Salmonella enteritidis disseminated infection. J. Clin. Investig. 102(12):2035-40
8. Raju R, Peters BS, Breen RA. 2012. Lung infections in the HIV-infected adult. Curr. Opin. Pulm. Med. 18(3):253-58
9. van de Veerdonk FL, Netea MG. 2010. T-cell subsets and antifungal host defenses. Curr. Fungal Infect. Rep. 4(4):238-43
10. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. 1986. Two types of murine helper Tcell clone. I.Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136(7):2348-57
11. Khader SA, Guglani L, Rangel-Moreno J, Gopal R, Junecko BA, et al. 2011. IL-23 is required for longterm control of Mycobacterium tuberculosis and B cell follicle formation in the infected lung. J. Immunol. 187(10):5402-7
12. Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL. 2003. Interleukin-23 promotes a distinct CD4Tcell activation state characterized by the production of interleukin-17. J. Biol. Chem. 278(3):1910-14
13. Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, et al. 2003. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421(6924):744-48
14. Harrington LE, Hatton RD, Mangan PR, TurnerH, Murphy TL, et al. 2005. Interleukin 17-producing CD4+ effectorTcells develop via a lineage distinct from theThelper type 1 and 2 lineages. Nat. Immunol. 6(11):1123-32
15. Murphy CA, LangrishCL, Chen Y, BlumenscheinW, McClanahan T, et al. 2003. Divergent pro-and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J. Exp.Med. 198(12):1951-57
16. Park H, Li Z, Yang XO, Chang SH, Nurieva R, et al. 2005. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol. 6(11):1133-41
17. Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B. 2006. TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24(2):179-89
18. Infante-Duarte C, Horton HF, Byrne MC, Kamradt T. 2000. Microbial lipopeptides induce the production of IL-17 in Th cells. J. Immunol. 165:6107-15
19. Suárez-Méndez R, Garcá-Garcá I, Fernández-Olivera N, Valdés-Quintana M, Milanés-Virelles MT, et al. 2004. Adjuvant interferon gamma in patients with drug-resistant pulmonary tuberculosis: a pilot study. BMC Infect. Dis. 4:44
20. Chen W, Jin W, Hardegen N, Lei KJ, Li L, et al. 2003. Conversion of peripheral CD4+CD25-naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3. J. Exp. Med. 198(12):1875-86
21. Fu S, Zhang N, Yopp AC, Chen D, Mao M, et al. 2004. TGF-β induces Foxp3+ T-regulatory cells from CD4+ CD25-precursors. Am. J. Transplant. 4(10):1614-27
22. FantiniMC, Becker C, Monteleone G, Pallone F, Galle PR, et al. 2004. Cutting edge: TGF-βinduces a regulatory phenotype in CD4+CD25-T cells through Foxp3 induction and down-regulation of Smad7. J. Immunol. 172(9):5149-53
23. Zheng SG, Wang JH, Gray JD, Soucier H, Horwitz DA. 2004. Natural and induced CD4+CD25+ cells educate CD4+CD25-cells to develop suppressive activity: the role of IL-2, TGF-β, and IL-10. J. Immunol. 172(9):5213-21
24. Newport MJ, Huxley CM, Huston S, Hawrylowicz CM, Oostra BA, et al. 1996. A mutation in the interferon-γ-receptor gene and susceptibility to mycobacterial infection. N. Engl. J.Med. 335(26):1941-49
25. Elloumi-Zghal H, Barbouche MR, Chemli J, Bejaoui M, Harbi A, et al. 2002. Clinical and genetic heterogeneity of inherited autosomal recessive susceptibility to disseminated Mycobacterium bovis bacille Calmette- Guérin infection. J. Infect. Dis. 185(10):1468-75
26. de Jong R, Altare F, Haagen IA, Elferink DG, Boer T, et al. 1998. Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. Science 280(5368):1435-38
27. Sakai T, Matsuoka M, Aoki M, Nosaka K, Mitsuya H. 2001. Missense mutation of the interleukin-12 receptor β1 chain-encoding gene is associated with impaired immunity against Mycobacterium avium complex infection. Blood 97(9):2688-94
28. Ottenhoff TH, Verreck FA, Lichtenauer-Kaligis EG, Hoeve MA, Sanal O, et al. 2002. Genetics, cytokines and human infectious disease: lessons from weakly pathogenic mycobacteria and salmonellae. Nat. Genet. 32(1):97-105
29. Getahun H, Gunneberg C, Granich R, Nunn P. 2010. HIV infection-associated tuberculosis: the epidemiology and the response. Clin. Infect. Dis. 50(Suppl. 3):S201-7
30. Bal AM, Lakhashe SK, ThakarMR, Tripathy SP, Paranjape RS. 2005. Dysregulation of proinflammatory and regulatory cytokines in HIV infected persons with active tuberculosis. Cytokine 30:275-81
31. Wolf AJ, Linas B, Trevejo-Nunez GJ, Kincaid E, Tamura T, et al. 2007. Mycobacterium tuberculosis infects dendritic cells with high frequency and impairs their function in vivo. J. Immunol. 179(4):2509-19
32. Reiley WW, Calayag MD, Wittmer ST, Huntington JL, Pearl JE, et al. 2008. ESAT-6-specific CD4 T cell responses to aerosol Mycobacterium tuberculosis infection are initiated in the mediastinal lymph nodes. Proc. Natl. Acad. Sci. USA 105(31):10961-66
33. Chackerian AA, Perera TV, Behar SM. 2001. Gamma interferon-producingCD4+ Tlymphocytes in the lung correlate with resistance to infection with Mycobacterium tuberculosis. Infect. Immun. 69(4):2666-74
34. Egen JG, Rothfuchs AG, Feng CG, Horwitz MA, Sher A, et al. 2011. Intravital imaging reveals limited antigen presentation and T cell effector function in mycobacterial granulomas. Immunity 34(5):807-19
35. Gallegos AM, Pamer EG, Glickman MS. 2008. Delayed protection by ESAT-6-specific effector CD4+ T cells after airborne M. tuberculosis infection. J. Exp. Med. 205(10):2359-68
36. Reece ST, Kaufmann SH. 2012. Floating between the poles of pathology and protection: can we pin down the granuloma in tuberculosis? Curr. Opin. Microbiol. 15(1):63-70
37. Gallegos AM, van Heijst JW, Samstein M, Su X, Pamer EG, et al. 2011. A interferon independent mechanism ofCD4Tcellmediated control of M. tuberculosis infection in vivo. PLoS Pathog. 7(5):e1002052
38. Nandi B, Behar SM. 2011. Regulation of neutrophils by interferon-γ limits lung inflammation during tuberculosis infection. J. Exp. Med. 208(11):2251-62
39. Shams H, Wizel B, Weis SE, Samten B, Barnes PF. 2001. Contribution of CD8+ T cells to γinterferon production in human tuberculosis. Infect. Immun. 69(5):3497-501
40. Geldmacher C, Schuetz A, Ngwenyama N, Casazza JP, Sanga E, et al. 2008. Early depletion of Mycobacterium tuberculosis-specific T helper 1 cell responses afterHIV-1 infection. J. Infect. Dis. 198(11):1590-98
41. MetzgerDW, Bakshi CS, KirimanjeswaraG. 2007. Mucosal immunopathogenesis of Francisella tularensis. Ann. N. Y. Acad. Sci. 1105:266-83
42. Geng Y, Berencsi K, Gyulai Z, Valyi-Nagy T, Gonczol E, et al. 2000. Roles of interleukin-12 and γ interferon in murine Chlamydia pneumoniae infection. Infect. Immun. 68(4):2245-53
43. Deng JC, Moore TA, Newstead MW, Zeng X, Krieg AM, et al. 2004. CpG oligodeoxynucleotides stimulate protective innate immunity against pulmonary Klebsiella infection. J. Immunol. 173(8):5148-55
44. Deng JC, Zeng X, NewsteadM, Moore TA, Tsai WC, et al. 2004. STAT4 is a critical mediator of early innate immune responses against pulmonary Klebsiella infection. J. Immunol. 173(6):4075-83
45. Condos R, Rom WN, Schluger NW. 1997. Treatment of multidrug-resistant pulmonary tuberculosis with interferon-γvia aerosol. Lancet 349(9064):1513-15
46. Milanées-Virelles MT, Garcá-Garcá I, Santos-Herrera Y, Valdés-Quintana M, Valenzuela-Silva CM, et al. 2008. Adjuvant interferon γ in patients with pulmonary atypical Mycobacteriosis: a randomized, double-blind, placebo-controlled study. BMC Infect. Dis. 8:17
47. Deng JC, Tateda K, Zeng X, Standiford TJ. 2001. Transient transgenic expression of γ interferon promotes Legionella pneumophila clearance in immunocompetent hosts. Infect. Immun. 69(10):6382-90
48. LettingaKD, Weijer S, Speelman P, Prins JM, Van Der PollT, et al. 2003. Reduced interferon-γrelease in patients recovered from Legionnaires' disease. Thorax 58(1):63-67
49. WHO. 2009. Influenza. Fact Sheet No. 211, April. WHO, Geneva. http://www.who.int/mediacentre/factsheets/fs211/en/index.html
50. Guo H, Santiago F, Lambert K, Takimoto T, Topham DJ. 2011. T cell-mediated protection against lethal 2009 pandemic H1N1 influenza virus infection in a mouse model. J. Virol. 85(1):448-55
51. Sun K, Ye J, Perez DR, Metzger DW. 2011. Seasonal FluMist vaccination induces cross-reactive T cell immunity against H1N1 2009 influenza and secondary bacterial infections. J. Immunol. 186(2):987-93
52. Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, et al. 2009. The burden of respiratory syncytial virus infection in young children. N. Engl. J. Med. 360(6):588-98
53. Cautivo KM, Bueno SM, Cortes CM, Wozniak A, Riedel CA, et al. 2010. Efficient lung recruitment of respiratory syncytial virus-specificTh1 cells induced by recombinant bacillusCalmette-Guérin promotes virus clearance and protects from infection. J. Immunol. 185(12):7633-45
54. RippleMJ, YouD, Honnegowda S, Giaimo JD, Sewell AB, et al. 2010. Immunomodulation with IL-4R? antisense oligonucleotide prevents respiratory syncytial virus-mediated pulmonary disease. J. Immunol. 185(8):4804-11
55. Empey KM, Orend JG, Peebles RS Jr, Egana L, Norris KA, et al. 2012. Stimulation of immature lung macrophages with intranasal interferon gamma in a novel neonatal mouse model of respiratory syncytial virus infection. PLoS ONE 7(7):e40499
56. Romani L, Puccetti P, Bistoni F. 1997. Interleukin-12 in infectious diseases. Clin. Microbiol. Rev. 10(4):611-36
57. Chen GH, McDonald RA, Wells JC, Huffnagle GB, Lukacs NW, et al. 2005. The γinterferon receptor is required for the protective pulmonary inflammatory response to Cryptococcus neoformans. Infect. Immun. 73(3):1788-96
58. Herring AC, Lee J, McDonald RA, Toews GB, Huffnagle GB. 2002. Induction of interleukin-12 and γ interferon requires tumor necrosis factor-for protective T1-cell-mediated immunity to pulmonary Cryptococcus neoformans infection. Infect. Immun. 70(6):2959-64
59. Hebart H, BollingerC, Fisch P, Sarfati J, Meisner C, et al. 2002. Analysis ofT-cell responses to Aspergillus fumigatus antigens in healthy individuals and patientswith hematologicmalignancies. Blood 100(13):4521-28
60. Beck JM, Liggitt HD, Brunette EN, Fuchs HJ, Shellito JE, et al. 1991. Reduction in intensity of Pneumocystis carinii pneumonia in mice by aerosol administration of γinterferon. Infect. Immun. 59(11):3859-62
61. Garvy BA, Wiley JA, Gigliotti F, Harmsen AG. 1997. Protection against Pneumocystis carinii pneumonia by antibodies generated from either T helper 1 or T helper 2 responses. Infect. Immun. 65(12):5052-56
62. Magee DM, Cox RA. 1995. Roles of γinterferon and interleukin-4 in genetically determined resistance to Coccidioides immitis. Infect. Immun. 63(9):3514-19
63. Magee DM, Cox RA. 1996. Interleukin-12 regulation of host defenses against Coccidioides immitis. Infect. Immun. 64(9):3609-13
64. Wu-Hsieh BA, Howard DH. 1987. Inhibition of the intracellular growth of Histoplasma capsulatum by recombinant murine γinterferon. Infect. Immun. 55(4):1014-16
65. Clemons KV, Darbonne WC, Curnutte JT, Sobel RA, Stevens DA. 2000. Experimental histoplasmosis in mice treated with anti-murine interferon-γantibody and in interferon-γgene knockout mice. Microbes Infect. 2(9):997-1001
66. Williams CM, Rahman S, Hubeau C, Ma HL. 2012. Cytokine pathways in allergic disease. Toxicol. Pathol. 40(2):205-15
67. Yadava K, Sichelstiel A, Luescher IF, Nicod LP, Harris NL, Marsland BJ. 2012. TSLP promotes influenza-specific CD8+ T-cell responses by augmenting local inflammatory dendritic cell function. Mucosal Immunol. 6(1):83-92
68. Chang YJ, Kim HY, Albacker LA, Baumgarth N, McKenzie AN, et al. 2011. Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity. Nat. Immunol. 12(7):631-38
69. Kaiko GE, Phipps S, Angkasekwinai P, Dong C, Foster PS. 2010. NK cell deficiency predisposes to viral-induced Th2-type allergic inflammation via epithelial-derived IL-25. J. Immunol. 185(8):4681-90
70. Vijayan VK. 2007. How to diagnose and manage common parasitic pneumonias. Curr. Opin. Pulm. Med. 13(3):218-24
71. Kolosionek E, Crosby A, Harhay MO, Morrell N, Butrous G. 2010. Pulmonary vascular disease associated with schistosomiasis. Expert Rev. Anti-Infect. Ther. 8(12):1467-73
72. Chen F, Liu Z, WuW, Rozo C, Bowdridge S, et al. 2012. An essential role for TH2-type responses in limiting acute tissue damage during experimental helminth infection. Nat. Med. 18(2):260-66
73. Bush RK. 2012. Parasites and allergic disease: another piece of the puzzle. J. Allergy Clin. Immunol. 130(1):257-58
74. Potian JA, RafiW, Bhatt K, McBride A, Gause WC, et al. 2011. Preexisting helminth infection induces inhibition of innate pulmonary anti-tuberculosis defense by engaging the IL-4 receptor pathway. J. Exp. Med. 208(9):1863-74
75. Swain SL, McKinstry KK, Strutt TM. 2012. Expanding roles for CD4+ T cells in immunity to viruses. Nat. Rev. Immunol. 12(2):136-48
76. Marshall D, Sealy R, Sangster M, Coleclough C. 1999. TH cells primed during influenza virus infection provide help for qualitatively distinct antibody responses to subsequent immunization. J. Immunol. 163(9):4673-82
77. Clements ML, Betts RF, Tierney EL, Murphy BR. 1986. Serum and nasal wash antibodies associated with resistance to experimental challengewith influenza A wild-type virus. J. Clin.Microbiol. 24(1):157-60
78. Palladino G, Mozdzanowska K, Washko G, Gerhard W. 1995. Virus-neutralizing antibodies of immunoglobulin G (IgG) but not of IgM or IgA isotypes can cure influenza virus pneumonia in SCID mice. J. Virol. 69(4):2075-81
79. Renegar KB, Small PA Jr, Boykins LG, Wright PF. 2004. Role of IgA versus IgG in the control of influenza viral infection in the murine respiratory tract. J. Immunol. 173(3):1978-86
80. Collins PL, Graham BS. 2008. Viral and host factors in human respiratory syncytial virus pathogenesis. J. Virol. 82(5):2040-55
81. KimHW, Canchola JG, BrandtCD, Pyles G, ChanockRM, et al. 1969. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am. J. Epidemiol. 89(4):422-34
82. Romani L. 2004. Immunity to fungal infections. Nat. Rev. Immunol. 4(1):1-23
83. Kreindler JL, Steele C, Nguyen N, Chan YR, Pilewski JM, et al. 2010. Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis. J. Clin. Investig. 120(9):3242-54
84. Cenci E, Mencacci A, Del Sero G, Bacci A, Montagnoli C, et al. 1999. Interleukin-4 causes susceptibility to invasive pulmonary aspergillosis through suppression of protective type I responses. J. Infect. Dis. 180(6):1957-68
85. Kling HM, Shipley TW, Patil SP, Kristoff J, Bryan M, et al. 2010. Relationship of Pneumocystis jiroveci humoral immunity to prevention of colonization and chronic obstructive pulmonary disease in a primate model of HIV infection. Infect. Immun. 78(10):4320-30
86. Rapaka RR, Ricks DM, Alcorn JF, Chen K, Khader SA, et al. 2010. Conserved natural IgM antibodies mediate innate and adaptive immunity against the opportunistic fungus Pneumocystis murina. J. Exp.Med. 207(13):2907-19
87. Ye P, Rodriguez FH, Kanaly S, Stocking KL, Schurr J, et al. 2001. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J. Exp. Med. 194(4):519-27
88. Wu Q, Martin RJ, Rino JG, Breed R, Torres RM, et al. 2007. IL-23-dependent IL-17 production is essential in neutrophil recruitment and activity in mouse lung defense against respiratory Mycoplasma pneumoniae infection. Microbes Infect. 9(1):78-86
89. Happel KI, Dubin PJ, Zheng M, Ghilardi N, Lockhart C, et al. 2005. Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae. J. Exp. Med. 202(6):761-69
90. Khader SA, Pearl JE, Sakamoto K, Gilmartin L, Bell GK, et al. 2005. IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-γresponses if IL-12p70 is available. J. Immunol. 175(2):788-95
91. Sun K, Metzger DW. 2008. Inhibition of pulmonary antibacterial defense by interferon-γ during recovery from influenza infection. Nat. Med. 14(5):558-64
92. Khader SA, Bell GK, Pearl JE, Fountain JJ, Rangel-Moreno J, et al. 2007. IL-23 and IL-17 in the establishment of protective pulmonaryCD4+ Tcell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat. Immunol. 8(4):369-77
93. WozniakTM, Ryan AA, BrittonWJ. 2006. Interleukin-23 restores immunity to Mycobacterium tuberculosis infection in IL-12p40-deficient mice and is not required for the development of IL-17-secreting T cell responses. J. Immunol. 177(12):8684-92
94. Wozniak TM, Ryan AA, Triccas JA, BrittonWJ. 2006. Plasmid interleukin-23 (IL-23), but not plasmid IL-27, enhances the protective efficacy of a DNA vaccine against Mycobacterium tuberculosis infection. Infect. Immun. 74(1):557-65
95. Koch R. 1891. A further communication on a remedy for tuberculosis. Br. Med. J. 1(1568):125-27
96. Cruz A, Fraga AG, Fountain JJ, Rangel-Moreno J, Torrado E, et al. 2010. Pathological role of interleukin 17 in mice subjected to repeated BCG vaccination after infection with Mycobacterium tuberculosis. J. Exp. Med. 207(8):1609-16
97. Lin Y, Ritchea S, Logar A, Slight S, MessmerM, et al. 2009. Interleukin-17 is required forThelper 1 cell immunity and host resistance to the intracellular pathogen Francisella tularensis. Immunity 31(5):799-810
98. Dubin PJ, Martz A, Eisenstatt JR, FoxMD, Logar A, et al. 2012. Interleukin-23-mediated inflammation in Pseudomonas aeruginosa pulmonary infection. Infect. Immun. 80(1):398-409
99. Kudva A, Scheller EV, Robinson KM, Crowe CR, Choi SM, et al. 2011. Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice. J. Immunol. 186(3):1666-74
100. Chen K, McAleer JP, Lin Y, Paterson DL, Zheng M, et al. 2011. Th17 cells mediate clade-specific, serotype-independent mucosal immunity. Immunity 35(6):997-1009
101. Moffitt KL, Gierahn TM, Lu YJ, Gouveia P, Alderson M, et al. 2011. T(H)17-based vaccine design for prevention of Streptococcus pneumoniae colonization. Cell Host Microbe 9(2):158-65
102. Priebe GP, Walsh RL, Cederroth TA, Kamei A, Coutinho-Sledge YS, et al. 2008. IL-17 is a critical component of vaccine-induced protection against lung infection by lipopolysaccharide-heterologous strains of Pseudomonas aeruginosa. J. Immunol. 181(7):4965-75
103. Brown DM, Lee S, Garcia-HernandezMde L, Swain SL. 2012. Multifunctional CD4 cells expressing γ interferon and perforin mediate protection against lethal influenza virus infection. J. Virol. 86(12):6792-803
104. Crowe CR, Chen K, Pociask DA, Alcorn JF, Krivich C, et al. 2009. Critical role of IL-17RA in immunopathology of influenza infection. J. Immunol. 183(8):5301-10
105. Mukherjee S, Lindell DM, Berlin AA, Morris SB, Shanley TP, et al. 2011. IL-17-induced pulmonary pathogenesis during respiratory viral infection and exacerbation of allergic disease. Am. J. Pathol 179(1):248-58
106. Huang W, Na L, Fidel PL, Schwarzenberger P. 2004. Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice. J. Infect. Dis. 190(3):624-31
107. Gaffen SL, Hernandez-Santos N, Peterson AC. 2011. IL-17 signaling in host defense against Candida albicans. Immunol. Res. 50(2-3):181-87
108. Hardison SE, Wozniak KL, Kolls JK, Wormley FL Jr. 2010. Interleukin-17 is not required for classical macrophage activation in a pulmonary mouse model of Cryptococcus neoformans infection. Infect. Immun. 78(12):5341-51
109. Huffnagle GB, Lipscomb MF. 1998. Cells and cytokines in pulmonary cryptococcosis. Res. Immunol. 149(4-5):387-514
110. Chai LY, van de Veerdonk F, Marijnissen RJ, Cheng SC, Khoo AL, et al. 2010. Anti-Aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity. Immunology 130(1):46-54
111. Chan YR, Chen K, Duncan SR, Lathrop KL, Latoche JD, et al. 2012. Patients with cystic fibrosis have inducible IL-17+IL-22+ memory cells in lung draining lymph nodes. J. Allergy Clin. Immunol. In press
112. Zelante T, De Luca A, Bonifazi P, Montagnoli C, Bozza S, et al. 2007. IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur. J. Immunol. 37(10):2695-706
113. Rudner XL, Happel KI, Young EA, Shellito JE. 2007. Interleukin-23 (IL-23)-IL-17 cytokine axis in murine Pneumocystis carinii infection. Infect. Immun. 75(6):3055-61
114. Ghoreschi K, Laurence A, Yang XP, Tato CM, McGeachy MJ, et al. 2010. Generation of pathogenic T(H)17 cells in the absence of TGF-βsignalling. Nature 467(7318):967-71
115. Wuthrich M, Gern B, Hung CY, Ersland K, Rocco N, et al. 2011. Vaccine-induced protection against 3 systemic mycoses endemic to North America requiresTh17 cells in mice. J. Clin. Investig. 121(2):554-68
116. Wuthrich M, Hung CY, Gern BH, Pick-Jacobs JC, Galles KJ, et al. 2011. A TCR transgenic mouse reactive with multiple systemic dimorphic fungi. J. Immunol. 187(3):1421-31
117. Malley R, Srivastava A, Lipsitch M, Thompson CM, Watkins C, et al. 2006. Antibody-independent, interleukin-17A-mediated, cross-serotype immunity to pneumococci in mice immunized intranasally with the cell wall polysaccharide. Infect. Immun. 74(4):2187-95
118. Zhang Z, Clarke TB, Weiser JN. 2009. Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. J. Clin. Investig. 119(7):1899-909
119. Aujla SJ, Chan YR, Zheng M, FeiM, Askew DJ, et al. 2008. IL-22mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat. Med. 14(3):275-81
120. Guo H, Topham DJ. 2010. Interleukin-22 (IL-22) production by pulmonary natural killer cells and the potential role of IL-22 during primary influenza virus infection. J. Virol. 84(15):7750-59
121. Kumar P, ThakarMS, Ouyang W, Malarkannan S. 2012. IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection. Mucosal Immunol. In press
122. Paget C, Ivanov S, Fontaine J, Renneson J, Blanc F, et al. 2012. Interleukin-22 is produced by invariant natural killer T lymphocytes during influenza A virus infection: potential role in protection against lung epithelial damages. J. Biol. Chem. 287(12):8816-29
123. Gessner MA, Werner JL, Lilly LM, NelsonMP, Metz AE, et al. 2012. Dectin-1-dependent interleukin-22 contributes to early innate lung defense against Aspergillus fumigatus. Infect. Immun. 80(1):410-17
124. Myers AK, Perroni L, Costigan C, Reardon W. 2006. Clinical andmolecular findings in IPEX syndrome. Arch. Dis. Child. 91(1):63-64
125. Bilate AM, Lafaille JJ. 2012. Induced CD4+Foxp3+ regulatory T cells in immune tolerance. Annu. Rev. Immunol. 30:733-58
126. Crother TR, Schroder NW, Karlin J, Chen S, Shimada K, et al. 2011. Chlamydia pneumoniae infection induced allergic airway sensitization is controlled by regulatory T-cells and plasmacytoid dendritic cells. PLoS ONE 6(6):e20784
127. Carrigan SO, Yang YJ, Issekutz T, Forward N, Hoskin D, et al. 2009. Depletion of natural CD4+CD25+ Tregulatory cells with anti-CD25 antibody does not change the course of Pseudomonas aeruginosa-induced acute lung infection in mice. Immunobiology 214(3):211-22
128. Guyot-Revol V, Innes JA, Hackforth S, Hinks T, Lalvani A. 2006. Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis. Am. J. Respir. Crit. CareMed. 173(7):803-10
129. Quinn KM, McHugh RS, Rich FJ, Goldsack LM, de Lisle GW, et al. 2006. Inactivation of CD4+ CD25+ regulatory T cells during early mycobacterial infection increases cytokine production but does not affect pathogen load. Immunol. Cell Biol. 84(5):467-74
130. Quinn KM, Rich FJ, Goldsack LM, de Lisle GW, Buddle BM, et al. 2008. Accelerating the secondary immune response by inactivating CD4+CD25+ T regulatory cells prior to BCG vaccination does not enhance protection against tuberculosis. Eur. J. Immunol. 38(3):695-705
131. Jaron B, Maranghi E, Leclerc C, Majlessi L. 2008. Effect of attenuation of Treg during BCG immunization on anti-mycobacterial Th1 responses and protection against Mycobacterium tuberculosis. PLoS ONE 3(7):e2833
132. Paula MO, Fonseca DM, Wowk PF, Gembre AF, Fedatto PF, et al. 2011. Host genetic background affects regulatory T-cell activity that influences the magnitude of cellular immune response against Mycobacterium tuberculosis. Immunol. Cell Biol. 89(4):526-34
133. Betts RJ, Prabhu N, Ho AW, Lew FC, Hutchinson PE, et al. 2012. Influenza A virus infection results in a robust, antigen-responsive, and widely disseminated Foxp3+ regulatory T cell response. J. Virol. 86(5):2817-25
134. Betts RJ, Ho AW, Kemeny DM. 2011. Partial depletion of natural CD4+CD25+ regulatory T cells with anti-CD25 antibody does not alter the course of acute influenza A virus infection. PLoS ONE 6(11):e27849
135. Piersma SJ, van der Hulst JM, Kwappenberg KM, Goedemans R, van der Minne CE, van der Burg SH. 2010. Influenza matrix 1-specific human CD4+ FOXP3+ and FOXP3-regulatory T cells can be detected long after viral clearance. Eur. J. Immunol. 40(11):3064-74
136. Antunes I, Kassiotis G. 2010. Suppression of innate immune pathology by regulatory T cells during Influenza A virus infection of immunodeficient mice. J. Virol. 84(24):12564-75
137. Fulton RB, Meyerholz DK, Varga SM. 2010. Foxp3+ CD4 regulatory T cells limit pulmonary immunopathology by modulating the CD8 T cell response during respiratory syncytial virus infection. J. Immunol. 185(4):2382-92
138. Ruckwardt TJ, Bonaparte KL, NasonMC, Graham BS. 2009. Regulatory T cells promote early influx of CD8+ T cells in the lungs of respiratory syncytial virus-infected mice and diminish immunodominance disparities. J. Virol. 83(7):3019-28
139. Loures FV, Pina A, Felonato M, Araujo EF, Leite KR, et al. 2010. Toll-like receptor 4 signaling leads to severe fungal infection associated with enhanced proinflammatory immunity and impaired expansion of regulatory T cells. Infect. Immun. 78(3):1078-88
140. Hori S, Carvalho TL, Demengeot J. 2002. CD25+CD4+ regulatory T cells suppress CD4+ T cellmediated pulmonary hyperinflammation driven by Pneumocystis carinii in immunodeficient mice. Eur. J. Immunol. 32(5):1282-91
141. McKinley L, Logar AJ, McAllister F, Zheng M, Steele C, et al. 2006. Regulatory T cells dampen pulmonary inflammation and lung injury in an animal model of pneumocystis pneumonia. J. Immunol. 177(9):6215-26
142. Murdoch DM, Venter WD, Van Rie A, Feldman C. 2007. Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options. AIDS Res. Ther. 4:9
143. Worsley CM, SuchardMS, StevensWS, Van Rie A, Murdoch DM. 2010. Multi-analyte profiling of ten cytokines in South African HIV-infected patients with Immune Reconstitution Inflammatory Syndrome (IRIS). AIDS Res. Ther. 7:36
144. Schulze Zur Wiesch J, Thomssen A, Hartjen P, Toth I, Lehmann C, et al. 2011. Comprehensive analysis of frequency and phenotype of T regulatory cells in HIV infection: CD39 expression of FoxP3+ T regulatory cells correlates with progressive disease. J. Virol. 85(3):1287-97
145. Spolski R, Wang L, Wan CK, Bonville CA, Domachowske JB, et al. 2012. IL-21 promotes the pathologic immune response to pneumovirus infection. J. Immunol. 188(4):1924-32
146. Boyden AW, Legge KL, Waldschmidt TJ. 2012. Pulmonary infection with influenza a virus induces site-specific germinal center and T follicular helper cell responses. PLoS ONE 7(7):e40733
147. Ballesteros-Tato A, Leon B, Graf BA, Moquin A, Adams PS, et al. 2012. Interleukin-2 inhibits germinal center formation by limiting T follicular helper cell differentiation. Immunity 36(5):847-56
148. Nakayamada S, Kanno Y, Takahashi H, Jankovic D, Lu KT, et al. 2011. Early Th1 cell differentiation is marked by a Tfh cell-like transition. Immunity 35(6):919-31
149. Jiang J, Fisher EM, Murasko DM. 2011. CD8 T cell responses to influenza virus infection in aged mice. Ageing Res. Rev. 10(4):422-27
150. Peiris JS, Hui KP, Yen HL. 2010. Host response to influenza virus: protection versus immunopathology. Curr. Opin. Immunol. 22(4):475-81
151. Moskophidis D, Kioussis D. 1998. Contribution of virus-specific CD8+ cytotoxic T cells to virus clearance or pathologicmanifestations of influenza virus infection in aTcell receptor transgenicmousemodel. J. Exp. Med. 188(2):223-32
152. Chang J, Braciale TJ. 2002. Respiratory syncytial virus infection suppresses lung CD8+ T-cell effector activity and peripheral CD8+ T-cell memory in the respiratory tract. Nat. Med. 8(1):54-60
153. Olson MR, Varga SM. 2007. CD8 T cells inhibit respiratory syncytial virus (RSV) vaccine-enhanced disease. J. Immunol. 179(8):5415-24
154. Woodworth JS, Behar SM. 2006. Mycobacterium tuberculosis-specific CD8+ T cells and their role in immunity. Crit. Rev. Immunol. 26(4):317-52
155. Weber SE, Tian H, Pirofski LA. 2011. CD8+ cells enhance resistance to pulmonary serotype 3 Streptococcus pneumoniae infection in mice. J. Immunol. 186(1):432-42
156. Gohil SK, Heo M, Schoenbaum EE, Celentano D, Pirofski LA. 2012. CD8+ T cells and risk for bacterial pneumonia and all-cause mortality among HIV-infected women. J. Acquir. Immune Defic. Syndr. 60(2):191-98
157. Templeton SP, Buskirk AD, Law B, Green BJ, Beezhold DH. 2011. Role of germination in murine airway CD8+ T-cell responses to Aspergillus conidia. PLoS ONE 6(4):e18777
158. Chaudhary N, Staab JF, Marr KA. 2010. Healthy human T-cell responses to Aspergillus fumigatus antigens. PLoS ONE 5(2):e9036
159. CarvalhoA, De LucaA, Bozza S, Cunha C, D'Angelo C, et al. 2012.TLR3essentially promotes protective class I-restricted memory CD8+ T-cell responses to Aspergillus fumigatus in hematopoietic transplanted patients. Blood 119(4):967-77
160. McAllister F, Steele C, Zheng M, Young E, Shellito JE, et al. 2004. T cytotoxic-1 CD8+ T cells are effector cells against pneumocystis in mice. J. Immunol. 172(2):1132-38
161. Meissner NN, Lund FE, Han S, Harmsen A. 2005. CD8 T cell-mediated lung damage in response to the extracellular pathogen pneumocystis is dependent on MHC class I expression by radiation-resistant lung cells. J. Immunol. 175(12):8271-79
162. Hamada H, Garcia-Hernandez Mde L, Reome JB, Misra SK, Strutt TM, et al. 2009. Tc17, a unique subset of CD8 T cells that can protect against lethal influenza challenge. J. Immunol. 182(6):3469-81
163. Nanjappa SG, Heninger E, Wuthrich M, Gasper DJ, Klein BS. 2012. Tc17 cells mediate vaccine immunity against lethal fungal pneumonia in immune
164. Moore TA, Moore BB, Newstead MW, Standiford TJ. 2000. γ ∞-T cells are critical for survival and early proinflammatory cytokine gene expression duringmurine Klebsiella pneumonia. J. Immunol. 165(5):2643-50
165. Lockhart E, Green AM, Flynn JL. 2006. IL-17 production is dominated by γ ∞T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. J. Immunol. 177(7):4662-69
166. Nakasone C, Yamamoto N, Nakamatsu M, Kinjo T, Miyagi K, et al. 2007. Accumulation of γ/∞ T cells in the lungs and their roles in neutrophil-mediated host defense against pneumococcal infection. Microbes Infect. 9(3):251-58
167. Harding M, Kubes P. 2012. Innate immunity in the vasculature: interactions with pathogenic bacteria. Curr. Opin. Microbiol. 15(1):85-91
168. Paget C, Ivanov S, Fontaine J, Blanc F, PichavantM, et al. 2011. Potential role of invariantNKT cells in the control of pulmonary inflammation and CD8+ T cell response during acute influenza A virus H3N2 pneumonia. J. Immunol. 186(10):5590-602
169. Qin G, Liu Y, Zheng J, Ng IH, Xiang Z, et al. 2011. Type 1 responses of human Vγ9V-2 T cells to influenza A viruses. J. Virol. 85(19):10109-16
170. Monticelli LA, Sonnenberg GF, Artis D. 2012. Innate lymphoid cells: critical regulators of allergic inflammation and tissue repair in the lung. Curr. Opin. Immunol. 24(3):284-89
171. Kawakami K, Kinjo Y, Yara S, Koguchi Y, Uezu K, et al. 2001. Activation of Vα14+ natural killer T cells by α-galactosylceramide results in development of Th1 response and local host resistance in mice infected with Cryptococcus neoformans. Infect. Immun. 69(1):213-20
172. Uezu K, Kawakami K, Miyagi K, Kinjo Y, Kinjo T, et al. 2004. Accumulation of γ ∞T cells in the lungs and their regulatory roles in Th1 response and host defense against pulmonary infection with Cryptococcus neoformans. J. Immunol. 172(12):7629-34
173. Steele C, Zheng M, Young E, Marrero L, Shellito JE, et al. 2002. Increased host resistance against Pneumocystis carinii pneumonia in γ ∞ T-cell-deficient mice: protective role of γ interferon and CD8+ T cells. Infect. Immun. 70(9):5208-15
174. Blyth CC, Webb SA, Kok J, Dwyer DE, van Hal SJ, 2012. The impact of bacterial and viral co-infection in severe influenza. Influenza Other Respir. Viruses. In press
175. Seki M, Yanagihara K, Higashiyama Y, Fukuda Y, Kaneko Y, et al. 2004. Immunokinetics in severe pneumonia due to influenza virus and bacteria coinfection in mice. Eur. Respir. J. 24(1):143-49
176. Shahangian A, Chow EK, Tian X, Kang JR, Ghaffari A, et al. 2009. Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice. J. Clin. Investig. 119(7):1910-20
177. Hishiki H, Ishiwada N, Fukasawa C, Abe K, Hoshino T, et al. 2011. Incidence of bacterial coinfection with respiratory syncytial virus bronchopulmonary infection in pediatric inpatients. J. Infect. Chemother. 17(1):87-90
178. Papi A, Bellettato CM, Braccioni F, RomagnoliM, Casolari P, et al. 2006. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am. J. Respirat. Crit. CareMed. 173(10):1114-21
179. Pons J, Sauleda J, Ferrer JM, Barcelo B, Fuster A, et al. 2005. Blunted γ ∞ T-lymphocyte response in chronic obstructive pulmonary disease. Eur. Respir. J. 25(3):441-46
180. Knobloch J, Schild K, Jungck D, Urban K, Muller K, et al. 2011. The T-helper cell type 1 immune response to gram-negative bacterial infections is impaired in COPD. Am. J. Respirat. Crit. Care Med. 183(2):204-14
181. Shan M, Yuan X, Song LZ, Roberts L, Zarinkamar N, et al. 2012. Cigarette smoke induction of osteopontin (SPP1) mediates TH17 inflammation in human and experimental emphysema. Sci. Transl. Med. 4(117):117ra9
182. Wedzicha JA. 2004. Role of viruses in exacerbations of chronic obstructive pulmonary disease. Proc. Am. Thorac. Soc. 1(2):115-20
183. Shi L, Manthei DM, Guadarrama AG, Lenertz LY, Denlinger LC. 2012. Rhinovirus-induced IL-1β release from bronchial epithelial cells is independent of functional P2X7. Am. J. Respir. Cell Mol. Biol. 47(3):363-71
184. Wiehler S, Proud D. 2007. Interleukin-17A modulates human airway epithelial responses to human rhinovirus infection. Am. J. Physiol. Lung Cell. Mol. Physiol. 293(2):L505-15
185. McAllister F, Henry A, Kreindler JL, Dubin PJ, Ulrich L, et al. 2005. Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-and granulocyte colony-stimulating factor in bronchial epithelium: implications for airway inflammation in cystic fibrosis. J. Immunol. 175(1):404-12
186. Tan HL, Regamey N, Brown S, Bush A, Lloyd CM, et al. 2011. The Th17 pathway in cystic fibrosis lung disease. Am. J. Respir. Crit. Care Med. 184(2):252-58
187. Dinwiddie R. 2000. Pathogenesis of lung disease in cystic fibrosis. Respir. Int. Rev. Thorac. Dis. 67(1):3-8
188. Painter RG, Bonvillain RW, Valentine VG, Lombard GA, LaPlace SG, et al. 2008. The role of chloride anion and CFTR in killing of Pseudomonas aeruginosa by normal and CF neutrophils. J. Leukoc. Biol. 83(6):1345-53
189. Dubin PJ, Kolls JK. 2011. IL-17 in cystic fibrosis: more than just Th17 cells. Am. J. Respir. Crit. Care Med. 184(2):155-57
190. Pezzulo AA, Tang XX, HoeggerMJ, AlaiwaMH, Ramachandran S, et al. 2012. Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung. Nature 487(7405):109-13
191. Kreindler JL, Bertrand CA, Lee RJ, Karasic T, Aujla S, et al. 2009. Interleukin-17A induces bicarbonate secretion in normal human bronchial epithelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 296(2):L257-66
192. Gopal R, Lin Y, Obermajer N, Slight S, Nuthalapati N, et al. 2012. IL-23-dependent IL-17 drives Th1-cell responses following Mycobacterium bovis BCG vaccination. Eur. J. Immunol. 42(2):364-73
193. Nakayamada S, Takahashi H, Kanno Y, O'Shea JJ. 2012. Helper T cell diversity and plasticity. Curr. Opin. Immunol. 24(3):297-302