Balancing immune protection and immune pathology by CD8+ T-cell responses to influenza infection

Frontiers in Immunology

Volumn 7, Issue FEB, 2016, Pages

  Duan, Susu ^a   Thomas, Paul G ^a  

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

CD8+ T cells; Human; Immune regulation; Immunopathology; Influenza; Vaccination

Indexed keywords

CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CXCR3; INTERFERON; INTERLEUKIN 1BETA; INTERLEUKIN 6; PATHOGEN ASSOCIATED MOLECULAR PATTERN; PATTERN RECOGNITION RECEPTOR; TUMOR NECROSIS FACTOR ALPHA;

CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL INFILTRATION; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; CELLULAR DISTRIBUTION; CELLULAR IMMUNITY; CYTOKINE PRODUCTION; CYTOTOXICITY; DENDRITIC CELL; EFFECTOR CELL; HELPER CELL; IMMUNE RESPONSE; IMMUNOPATHOLOGY; INFLAMMATION; INFLUENZA; LYMPHOCYTE ACTIVATION; MAJOR HISTOCOMPATIBILITY COMPLEX; MEMORY T LYMPHOCYTE; NONHUMAN; REVIEW; VIRAL CLEARANCE;

EID: 84962587669     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2016.00025     Document Type: Review

References (124)

1. Wendel I, Matrosovich M, Klenk HD. Snapshot: evolution of human influenza A viruses. Cell Host Microbe (2015) 17:416. doi:10.1016/j.chom.2015.02.001.
2. Neumann G, Noda T, Kawaoka Y. Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature (2009) 459:931-9. doi:10.1038/nature08157.
3. Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, et al. Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med (2013) 368:1888-97. doi:10.1056/NEJMoa1304459.
4. Tripathi S, White MR, Hartshorn KL. The amazing innate immune response to influenza A virus infection. Innate Immun (2015) 21:73-98. doi:10.1177/1753425913508992.
5. Chiu C, Openshaw PJ. Antiviral B cell and T cell immunity in the lungs. Nat Immunol (2015) 16:18-26. doi:10.1038/ni.3056.
6. Lee BO, Rangel-Moreno J, Moyron-Quiroz JE, Hartson L, Makris M, Sprague F, et al. CD4 T cell-independent antibody response promotes resolution of primary influenza infection and helps to prevent reinfection. J Immunol (2005) 175:5827-38. doi:10.4049/jimmunol.175.9.5827.
7. Rangel-Moreno J, Carragher DM, Misra RS, Kusser K, Hartson L, Moquin A, et al. B cells promote resistance to heterosubtypic strains of influenza via multiple mechanisms. J Immunol (2008) 180:454-63. doi:10.4049/jimmunol.180.1.454.
8. Carragher DM, Kaminski DA, Moquin A, Hartson L, Randall TD. A novel role for non-neutralizing antibodies against nucleoprotein in facilitating resistance to influenza virus. J Immunol (2008) 181:4168-76. doi:10.4049/jimmunol.181.6.4168.
9. LaMere MW, Lam HT, Moquin A, Haynes L, Lund FE, Randall TD, et al. Contributions of antinucleoprotein IgG to heterosubtypic immunity against influenza virus. J Immunol (2011) 186:4331-9. doi:10.4049/jimmunol.1003057.
10. Laidlaw BJ, Decman V, Ali MA, Abt MC, Wolf AI, Monticelli LA, et al. Cooperativity between CD8+ T cells, non-neutralizing antibodies, and alveolar macrophages is important for heterosubtypic influenza virus immunity. PLoS Pathog (2013) 9:e1003207. doi:10.1371/journal.ppat.1003207.
11. Doherty PC, Turner SJ, Webby RG, Thomas PG. Influenza and the challenge for immunology. Nat Immunol (2006) 7:449-55. doi:10.1038/ni1343.
12. Iwasaki A, Pillai PS. Innate immunity to influenza virus infection. Nat Rev Immunol (2014) 14:315-28. doi:10.1038/nri3665.
13. Kim TH, Lee HK. Differential roles of lung dendritic cell subsets against respiratory virus infection. Immune Netw (2014) 14:128-37. doi:10.4110/in.2014.14.3.128.
14. Hao X, Kim TS, Braciale TJ. Differential response of respiratory dendritic cell subsets to influenza virus infection. J Virol (2008) 82:4908-19. doi:10.1128/JVI.02367-07.
15. Cella M, Jarrossay D, Facchetti F, Alebardi O, Nakajima H, Lanzavecchia A, et al. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med (1999) 5:919-23. doi:10.1038/11360.
16. Wolf AI, Buehler D, Hensley SE, Cavanagh LL, Wherry EJ, Kastner P, et al. Plasmacytoid dendritic cells are dispensable during primary influenza virus infection. J Immunol (2009) 182:871-9. doi:10.4049/jimmunol.182.2.871.
17. Boonnak K, Vogel L, Feldmann F, Feldmann H, Legge KL, Subbarao K. Lymphopenia associated with highly virulent H5N1 virus infection due to plasmacytoid dendritic cell-mediated apoptosis of T cells. J Immunol (2014) 192:5906-12. doi:10.4049/jimmunol.1302992.
18. Langlois RA, Legge KL. Plasmacytoid dendritic cells enhance mortality during lethal influenza infections by eliminating virus-specific CD8 T cells. J Immunol (2010) 184:4440-6. doi:10.4049/jimmunol.0902984.
19. GeurtsvanKessel CH, Willart MA, van Rijt LS, Muskens F, Kool M, Baas C, et al. Clearance of influenza virus from the lung depends on migratory langerin+CD11b-but not plasmacytoid dendritic cells. J Exp Med (2008) 205:1621-34. doi:10.1084/jem.20071365.
20. Kim TS, Braciale TJ. Respiratory dendritic cell subsets differ in their capacity to support the induction of virus-specific cytotoxic CD8+ T cell responses. PLoS One (2009) 4:e4204. doi:10.1371/journal.pone.0004204.
21. Heer AK, Harris NL, Kopf M, Marsland BJ. CD4+ and CD8+ T cells exhibit differential requirements for CCR7-mediated antigen transport during influenza infection. J Immunol (2008) 181:6984-94. doi:10.4049/jimmunol.181.10.6984.
22. Legge KL, Braciale TJ. Accelerated migration of respiratory dendritic cells to the regional lymph nodes is limited to the early phase of pulmonary infection. Immunity (2003) 18:265-77. doi:10.1016/S1074-7613(03)00023-2.
23. Yoon H, Legge KL, Sung SS, Braciale TJ. Sequential activation of CD8+ T cells in the draining lymph nodes in response to pulmonary virus infection. J Immunol (2007) 179:391-9. doi:10.4049/jimmunol.179.1.391.
24. Allan W, Tabi Z, Cleary A, Doherty PC. Cellular events in the lymph node and lung of mice with influenza. Consequences of depleting CD4+ T cells. J Immunol (1990) 144:3980-6.
25. Belz GT, Wodarz D, Diaz G, Nowak MA, Doherty PC. Compromised influenza virus-specific CD8(+)-T-cell memory in CD4(+)-T-cell-deficient mice. J Virol (2002) 76:12388-93. doi:10.1128/JVI.76.23.12388-12393.2002.
26. McGill J, Van RN, Legge KL. Protective influenza-specific CD8 T cell responses require interactions with dendritic cells in the lungs. J Exp Med (2008) 205:1635-46. doi:10.1084/jem.20080314.
27. McGill J, Van RN, Legge KL. IL-15 trans-presentation by pulmonary dendritic cells promotes effector CD8 T cell survival during influenza virus infection. J Exp Med (2010) 207:521-34. doi:10.1084/jem.20091711.
28. McGill J, Legge KL. Cutting edge: contribution of lung-resident T cell proliferation to the overall magnitude of the antigen-specific CD8 T cell response in the lungs following murine influenza virus infection. J Immunol (2009) 183:4177-81. doi:10.4049/jimmunol.0901109.
29. Kohlmeier JE, Miller SC, Smith J, Lu B, Gerard C, Cookenham T, et al. The chemokine receptor CCR5 plays a key role in the early memory CD8+ T cell response to respiratory virus infections. Immunity (2008) 29:101-13. doi:10.1016/j.immuni.2008.05.011.
30. Kohlmeier JE, Reiley WW, Perona-Wright G, Freeman ML, Yager EJ, Connor LM, et al. Inflammatory chemokine receptors regulate CD8(+) T cell contraction and memory generation following infection. J Exp Med (2011) 208:1621-34. doi:10.1084/jem.20102110.
31. Jelley-Gibbs DM, Dibble JP, Brown DM, Strutt TM, McKinstry KK, Swain SL. Persistent depots of influenza antigen fail to induce a cytotoxic CD8 T cell response. J Immunol (2007) 178:7563-70. doi:10.4049/jimmunol.178.12.7563.
32. Takamura S, Roberts AD, Jelley-Gibbs DM, Wittmer ST, Kohlmeier JE, Woodland DL. The route of priming influences the ability of respiratory virus-specific memory CD8+ T cells to be activated by residual antigen. J Exp Med (2010) 207:1153-60. doi:10.1084/jem.20090283.
33. Kim TS, Hufford MM, Sun J, Fu YX, Braciale TJ. Antigen persistence and the control of local T cell memory by migrant respiratory dendritic cells after acute virus infection. J Exp Med (2010) 207:1161-72. doi:10.1084/jem.20092017.
34. Zammit DJ, Turner DL, Klonowski KD, Lefrancois L, Cauley LS. Residual antigen presentation after influenza virus infection affects CD8 T cell activation and migration. Immunity (2006) 24:439-49. doi:10.1016/j.immuni.2006.01.015.
35. Kohlmeier JE, Miller SC, Woodland DL. Cutting edge: antigen is not required for the activation and maintenance of virus-specific memory CD8+ T cells in the lung airways. J Immunol (2007) 178:4721-5. doi:10.4049/jimmunol.178.8.4721.
36. Kaech SM, Cui W. Transcriptional control of effector and memory CD8+ T cell differentiation. Nat Rev Immunol (2012) 12:749-61. doi:10.1038/nri3307.
37. Yao S, Buzo BF, Pham D, Jiang L, Taparowsky EJ, Kaplan MH, et al. Interferon regulatory factor 4 sustains CD8(+) T cell expansion and effector differentiation. Immunity (2013) 39:833-45. doi:10.1016/j.immuni.2013.10.007.
38. Man K, Miasari M, Shi W, Xin A, Henstridge DC, Preston S, et al. The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells. Nat Immunol (2013) 14:1155-65. doi:10.1038/ni.2710.
39. Sun J, Dodd H, Moser EK, Sharma R, Braciale TJ. CD4+ T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs. Nat Immunol (2011) 12:327-34. doi:10.1038/ni.1996.
40. Cullen SP, Martin SJ. Mechanisms of granule-dependent killing. Cell Death Differ (2008) 15:251-62. doi:10.1038/sj.cdd.4402244.
41. Topham DJ, Tripp RA, Doherty PC. CD8+ T cells clear influenza virus by perforin or Fas-dependent processes. J Immunol (1997) 159:5197-200.
42. Ishikawa E, Nakazawa M, Yoshinari M, Minami M. Role of tumor necrosis factor-related apoptosis-inducing ligand in immune response to influenza virus infection in mice. J Virol (2005) 79:7658-63. doi:10.1128/JVI.79.12.7658-7663.2005.
43. Brincks EL, Katewa A, Kucaba TA, Griffith TS, Legge KL. CD8 T cells utilize TRAIL to control influenza virus infection. J Immunol (2008) 181:4918-25. doi:10.4049/jimmunol.181.10.7428-a.
44. Billiau A, Matthys P. Interferon-gamma: a historical perspective. Cytokine Growth Factor Rev (2009) 20:97-113. doi:10.1016/j.cytogfr.2009.02.004.
45. Brenner D, Blaser H, Mak TW. Regulation of tumour necrosis factor signalling: live or let die. Nat Rev Immunol (2015) 15:362-74. doi:10.1038/nri3834.
46. Peperzak V, Xiao Y, Veraar EA, Borst J. CD27 sustains survival of CTLs in virus-infected nonlymphoid tissue in mice by inducing autocrine IL-2 production. J Clin Invest (2010) 120:168-78. doi:10.1172/JCI40178.
47. Seder RA, Darrah PA, Roederer M. T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol (2008) 8:247-58. doi:10.1038/nri2274.
48. La Gruta NL, Turner SJ, Doherty PC. Hierarchies in cytokine expression profiles for acute and resolving influenza virus-specific CD8+ T cell responses: correlation of cytokine profile and TCR avidity. J Immunol (2004) 172:5553-60. doi:10.4049/jimmunol.172.9.5553.
49. Sun J, Madan R, Karp CL, Braciale TJ. Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nat Med (2009) 15:277-84. doi:10.1038/nm.1929.
50. Cerwenka A, Morgan TM, Harmsen AG, Dutton RW. Migration kinetics and final destination of type 1 and type 2 CD8 effector cells predict protection against pulmonary virus infection. J Exp Med (1999) 189:423-34. doi:10.1084/jem.189.2.423.
51. Wiley JA, Cerwenka A, Harkema JR, Dutton RW, Harmsen AG. Production of interferon-gamma by influenza hemagglutinin-specific CD8 effector T cells influences the development of pulmonary immunopathology. Am J Pathol (2001) 158:119-30. doi:10.1016/S0002-9440(10)63950-8.
52. Hamada H, Garcia-Hernandez ML, Reome JB, Misra SK, Strutt TM, McKinstry KK, et al. Tc17, a unique subset of CD8 T cells that can protect against lethal influenza challenge. J Immunol (2009) 182:3469-81. doi:10.4049/jimmunol.0801814.
53. Hamada H, Bassity E, Flies A, Strutt TM, Garcia-Hernandez ML, McKinstry KK, et al. Multiple redundant effector mechanisms of CD8+ T cells protect against influenza infection. J Immunol (2013) 190:296-306. doi:10.4049/jimmunol.1200571.
54. Yap KL, Ada GL, McKenzie IF. Transfer of specific cytotoxic T lymphocytes protects mice inoculated with influenza virus. Nature (1978) 273:238-9. doi:10.1038/273238a0.
55. Wells MA, Ennis FA, Albrecht P. Recovery from a viral respiratory infection. II. Passive transfer of immune spleen cells to mice with influenza pneumonia. J Immunol (1981) 126:1042-6.
56. Taylor PM, Askonas BA. Influenza nucleoprotein-specific cytotoxic T-cell clones are protective in vivo. Immunology (1986) 58:417-20.
57. Bender BS, Croghan T, Zhang L, Small PA Jr. Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge. J Exp Med (1992) 175:1143-5. doi:10.1084/jem.175.4.1143.
58. Eichelberger M, Allan W, Zijlstra M, Jaenisch R, Doherty PC. Clearance of influenza virus respiratory infection in mice lacking class I major histocompatibility complex-restricted CD8+ T cells. J Exp Med (1991) 174:875-80. doi:10.1084/jem.174.4.875.
59. Wells MA, Albrecht P, Ennis FA. Recovery from a viral respiratory infection. I. Influenza pneumonia in normal and T-deficient mice. J Immunol (1981) 126:1036-41.
60. Enelow RI, Mohammed AZ, Stoler MH, Liu AN, Young JS, Lou YH, et al. Structural and functional consequences of alveolar cell recognition by CD8(+) T lymphocytes in experimental lung disease. J Clin Invest (1998) 102:1653-61. doi:10.1172/JCI4174.
61. Zhao MQ, Stoler MH, Liu AN, Wei B, Soguero C, Hahn YS, et al. Alveolar epithelial cell chemokine expression triggered by antigen-specific cytolytic CD8(+) T cell recognition. J Clin Invest (2000) 106:R49-58. doi:10.1172/JCI9786.
62. Small BA, Dressel SA, Lawrence CW, Drake DR III, Stoler MH, Enelow RI, et al. CD8(+) T cell-mediated injury in vivo progresses in the absence of effector T cells. J Exp Med (2001) 194:1835-46. doi:10.1084/jem.194.12.1835.
63. Liu AN, Mohammed AZ, Rice WR, Fiedeldey DT, Liebermann JS, Whitsett JA, et al. Perforin-independent CD8(+) T-cell-mediated cytotoxicity of alveolar epithelial cells is preferentially mediated by tumor necrosis factor-alpha: relative insensitivity to Fas ligand. Am J Respir Cell Mol Biol (1999) 20:849-58. doi:10.1165/ajrcmb.20.5.3585.
64. Ramana CV, DeBerge MP, Kumar A, Alia CS, Durbin JE, Enelow RI. Inflammatory impact of IFN-gamma in CD8+ T cell-mediated lung injury is mediated by both Stat1-dependent and-independent pathways. Am J Physiol Lung Cell Mol Physiol (2015) 308:L650-7. doi:10.1152/ajplung.00360.2014.
65. Xu L, Yoon H, Zhao MQ, Liu J, Ramana CV, Enelow RI. Cutting edge: pulmonary immunopathology mediated by antigen-specific expression of TNF-alpha by antiviral CD8+ T cells. J Immunol (2004) 173:721-5. doi:10.4049/jimmunol.173.2.721.
66. DeBerge MP, Ely KH, Enelow RI. Soluble, but not transmembrane, TNF-alpha is required during influenza infection to limit the magnitude of immune responses and the extent of immunopathology. J Immunol (2014) 192:5839-51. doi:10.4049/jimmunol.1302729.
67. DeBerge MP, Ely KH, Cheng GS, Enelow RI. ADAM17-mediated processing of TNF-alpha expressed by antiviral effector CD8+ T cells is required for severe T-cell-mediated lung injury. PLoS One (2013) 8:e79340. doi:10.1371/journal.pone.0079340.
68. Srikiatkhachorn A, Chintapalli J, Liu J, Jamaluddin M, Harrod KS, Whitsett JA, et al. Interference with intraepithelial TNF-alpha signaling inhibits CD8(+) T-cell-mediated lung injury in influenza infection. Viral Immunol (2010) 23:639-45. doi:10.1089/vim.2010.0076.
69. Liu J, Zhao MQ, Xu L, Ramana CV, Declercq W, Vandenabeele P, et al. Requirement for tumor necrosis factor-receptor 2 in alveolar chemokine expression depends upon the form of the ligand. Am J Respir Cell Mol Biol (2005) 33:463-9. doi:10.1165/rcmb.2005-0204OC.
70. Seah SG, Carrington EM, Ng WC, Belz GT, Brady JL, Sutherland RM, et al. Unlike CD4+ T-cell help, CD28 costimulation is necessary for effective primary CD8+ T-cell influenza-specific immunity. Eur J Immunol (2012) 42:1744-54. doi:10.1002/eji.201142211.
71. Hashem AM, Gravel C, Chen Z, Yi Y, Tocchi M, Jaentschke B, et al. CD40 ligand preferentially modulates immune response and enhances protection against influenza virus. J Immunol (2014) 193:722-34. doi:10.4049/jimmunol.1300093.
72. Plumb AW, Patton DT, Seo JH, Loveday EK, Jean F, Ziegler SF, et al. Interleukin-7, but not thymic stromal lymphopoietin, plays a key role in the T cell response to influenza A virus. PLoS One (2012) 7:e50199. doi:10.1371/journal.pone.0050199.
73. Denton AE, Doherty PC, Turner SJ, La Gruta NL. IL-18, but not IL-12, is required for optimal cytokine production by influenza virus-specific CD8+ T cells. Eur J Immunol (2007) 37:368-75. doi:10.1002/eji.200636766.
74. McNally B, Ye F, Willette M, Flano E. Local blockade of epithelial PDL-1 in the airways enhances T cell function and viral clearance during influenza virus infection. J Virol (2013) 87:12916-24. doi:10.1128/JVI.02423-13.
75. Rutigliano JA, Sharma S, Morris MY, Oguin TH III, McClaren JL, Doherty PC, et al. Highly pathological influenza A virus infection is associated with augmented expression of PD-1 by functionally compromised virus-specific CD8+ T cells. J Virol (2014) 88:1636-51. doi:10.1128/JVI.02851-13.
76. Sharma S, Sundararajan A, Suryawanshi A, Kumar N, Veiga-Parga T, Kuchroo VK, et al. T cell immunoglobulin and mucin protein-3 (Tim-3)/Galectin-9 interaction regulates influenza A virus-specific humoral and CD8 T-cell responses. Proc Natl Acad Sci U S A (2011) 108:19001-6. doi:10.1073/pnas.1107087108.
77. Lin GH, Sedgmen BJ, Moraes TJ, Snell LM, Topham DJ, Watts TH. Endogenous 4-1BB ligand plays a critical role in protection from influenza-induced disease. J Immunol (2009) 182:934-47. doi:10.4049/jimmunol.182.2.934.
78. Humphreys IR, Walzl G, Edwards L, Rae A, Hill S, Hussell T. A critical role for OX40 in T cell-mediated immunopathology during lung viral infection. J Exp Med (2003) 198:1237-42. doi:10.1084/jem.20030351.
79. Erickson JJ, Gilchuk P, Hastings AK, Tollefson SJ, Johnson M, Downing MB, et al. Viral acute lower respiratory infections impair CD8+ T cells through PD-1. J Clin Invest (2012) 122:2967-82. doi:10.1172/JCI62860.
80. Zhou J, Matsuoka M, Cantor H, Homer R, Enelow RI. Cutting edge: engagement of NKG2A on CD8+ effector T cells limits immunopathology in influenza pneumonia. J Immunol (2008) 180:25-9. doi:10.4049/jimmunol.180.1.25.
81. Ely KH, Matsuoka M, DeBerge MP, Ruby JA, Liu J, Schneider MJ, et al. Tissue-protective effects of NKG2A in immune-mediated clearance of virus infection. PLoS One (2014) 9:e108385. doi:10.1371/journal.pone.0108385.
82. Brincks EL, Gurung P, Langlois RA, Hemann EA, Legge KL, Griffith TS. The magnitude of the T cell response to a clinically significant dose of influenza virus is regulated by TRAIL. J Immunol (2011) 187:4581-8. doi:10.4049/jimmunol.1002241.
83. Bertram EM, Lau P, Watts TH. Temporal segregation of 4-1BB versus CD28-mediated costimulation: 4-1BB ligand influences T cell numbers late in the primary response and regulates the size of the T cell memory response following influenza infection. J Immunol (2002) 168:3777-85. doi:10.4049/jimmunol.168.8.3777.
84. Hendriks J, Xiao Y, Borst J. CD27 promotes survival of activated T cells and complements CD28 in generation and establishment of the effector T cell pool. J Exp Med (2003) 198:1369-80. doi:10.1084/jem.20030916.
85. Hendriks J, Xiao Y, Rossen JW, van der Sluijs KF, Sugamura K, Ishii N, et al. During viral infection of the respiratory tract, CD27, 4-1BB, and OX40 collectively determine formation of CD8+ memory T cells and their capacity for secondary expansion. J Immunol (2005) 175:1665-76. doi:10.4049/jimmunol.175.3.1665.
86. Seah SG, Brady JL, Carrington EM, Ng WC, Sutherland RM, Hancock MS, et al. Influenza-induced, helper-independent CD8+ T cell responses use CD40 costimulation at the late phase of the primary response. J Leukoc Biol (2013) 93:145-54. doi:10.1189/jlb.0612266.
87. Johnson S, Zhan Y, Sutherland RM, Mount AM, Bedoui S, Brady JL, et al. Selected toll-like receptor ligands and viruses promote helper-independent cytotoxic T cell priming by upregulating CD40L on dendritic cells. Immunity (2009) 30:218-27. doi:10.1016/j.immuni.2008.11.015.
88. Pang IK, Ichinohe T, Iwasaki A. IL-1R signaling in dendritic cells replaces pattern-recognition receptors in promoting CD8(+) T cell responses to influenza A virus. Nat Immunol (2013) 14:246-53. doi:10.1038/ni.2514.
89. Crouse J, Kalinke U, Oxenius A. Regulation of antiviral T cell responses by type I interferons. Nat Rev Immunol (2015) 15:231-42. doi:10.1038/nri3806.
90. Redmond WL, Ruby CE, Weinberg AD. The role of OX40-mediated co-stimulation in T-cell activation and survival. Crit Rev Immunol (2009) 29:187-201. doi:10.1615/CritRevImmunol.v29.i3.10.
91. Vigano S, Banga R, Bellanger F, Pellaton C, Farina A, Comte D, et al. CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression. PLoS Pathog (2014) 10:e1004380. doi:10.1371/journal.ppat.1004380.
92. Yuen KY, Chan PK, Peiris M, Tsang DN, Que TL, Shortridge KF, et al. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet (1998) 351:467-71. doi:10.1016/S0140-6736(98)01182-9.
93. Verbist KC, Cole CJ, Field MB, Klonowski KD. A role for IL-15 in the migration of effector CD8 T cells to the lung airways following influenza infection. J Immunol (2011) 186:174-82. doi:10.4049/jimmunol.1002613.
94. Monteiro JM, Harvey C, Trinchieri G. Role of interleukin-12 in primary influenza virus infection. J Virol (1998) 72:4825-31.
95. Aldridge JR Jr, Moseley CE, Boltz DA, Negovetich NJ, Reynolds C, Franks J, et al. TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection. Proc Natl Acad Sci U S A (2009) 106:5306-11. doi:10.1073/pnas.0900655106.
96. Lim K, Hyun YM, Lambert-Emo K, Capece T, Bae S, Miller R, et al. Neutrophil trails guide influenza-specific CD8(+) T cells in the airways. Science (2015) 349:aaa4352. doi:10.1126/science.aaa4352.
97. Hufford MM, Richardson G, Zhou H, Manicassamy B, Garcia-Sastre A, Enelow RI, et al. Influenza-infected neutrophils within the infected lungs act as antigen presenting cells for anti-viral CD8(+) T cells. PLoS One (2012) 7:e46581. doi:10.1371/journal.pone.0046581.
98. Juno JA, Keynan Y, Fowke KR. Invariant NKT cells: regulation and function during viral infection. PLoS Pathog (2012) 8:e1002838. doi:10.1371/journal.ppat.1002838.
99. Paget C, Ivanov S, Fontaine J, Blanc F, Pichavant M, Renneson J, et al. Potential role of invariant NKT cells in the control of pulmonary inflammation and CD8+ T cell response during acute influenza A virus H3N2 pneumonia. J Immunol (2011) 186:5590-602. doi:10.4049/jimmunol.1002348.
100. Chappert P, Leboeuf M, Rameau P, Lalfer M, Desbois S, Liblau RS, et al. Antigen-specific Treg impair CD8(+) T-cell priming by blocking early T-cell expansion. Eur J Immunol (2010) 40:339-50. doi:10.1002/eji.200839107.
101. Hufford MM, Kim TS, Sun J, Braciale TJ. Antiviral CD8+ T cell effector activities in situ are regulated by target cell type. J Exp Med (2011) 208:167-80. doi:10.1084/jem.20101850.
102. Purbhoo MA, Irvine DJ, Huppa JB, Davis MM. T cell killing does not require the formation of a stable mature immunological synapse. Nat Immunol (2004) 5:524-30. doi:10.1038/ni0604-658a.
103. Faroudi M, Utzny C, Salio M, Cerundolo V, Guiraud M, Muller S, et al. Lytic versus stimulatory synapse in cytotoxic T lymphocyte/target cell interaction: manifestation of a dual activation threshold. Proc Natl Acad Sci U S A (2003) 100:14145-50. doi:10.1073/pnas.2334336100.
104. Valitutti S, Muller S, Dessing M, Lanzavecchia A. Different responses are elicited in cytotoxic T lymphocytes by different levels of T cell receptor occupancy. J Exp Med (1996) 183:1917-21. doi:10.1084/jem.183.4.1917.
105. CDC. Seasonal Influenza Q&A (2014). Available from: http://www.cdc.gov/flu/about/qa/disease.htm.
106. Grant EJ, Chen L, Quinones-Parra S, Pang K, Kedzierska K, Chen W. T-cell immunity to influenza A viruses. Crit Rev Immunol (2014) 34:15-39. doi:10.1615/CritRevImmunol.2013010019.
107. Grebe KM, Yewdell JW, Bennink JR. Heterosubtypic immunity to influenza A virus: where do we stand? Microbes Infect (2008) 10:1024-9. doi:10.1016/j.micinf.2008.07.002.
108. Hillaire ML, Osterhaus AD, Rimmelzwaan GF. Induction of virus-specific cytotoxic T lymphocytes as a basis for the development of broadly protective influenza vaccines. J Biomed Biotechnol (2011) 2011:939860. doi:10.1155/2011/939860.
109. Nguyen HH, Moldoveanu Z, Novak MJ, van Ginkel FW, Ban E, Kiyono H, et al. Heterosubtypic immunity to lethal influenza A virus infection is associated with virus-specific CD8(+) cytotoxic T lymphocyte responses induced in mucosa-associated tissues. Virology (1999) 254:50-60. doi:10.1006/viro.1998.9521.
110. O'Neill E, Krauss SL, Riberdy JM, Webster RG, Woodland DL. Heterologous protection against lethal A/HongKong/156/97 (H5N1) influenza virus infection in C57BL/6 mice. J Gen Virol (2000) 81:2689-96. doi:10.1099/0022-1317-81-11-2689.
111. Kreijtz JH, Bodewes R, van AG, Kuiken T, Fouchier RA, Osterhaus AD, et al. Primary influenza A virus infection induces cross-protective immunity against a lethal infection with a heterosubtypic virus strain in mice. Vaccine (2007) 25:612-20. doi:10.1016/j.vaccine.2006.08.036.
112. Kreijtz JH, Bodewes R, van den Brand JM, de MG, Baas C, van AG, et al. Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus. Vaccine (2009) 27:4983-9. doi:10.1016/j.vaccine.2009.05.079.
113. Weinfurter JT, Brunner K, Capuano SV III, Li C, Broman KW, Kawaoka Y, et al. Cross-reactive T cells are involved in rapid clearance of 2009 pandemic H1N1 influenza virus in nonhuman primates. PLoS Pathog (2011) 7:e1002381. doi:10.1371/journal.ppat.1002381.
114. Duan S, Meliopoulos VA, McClaren JL, Guo XZ, Sanders CJ, Smallwood HS, et al. Diverse heterologous primary infections radically alter immunodominance hierarchies and clinical outcomes following H7N9 influenza challenge in mice. PLoS Pathog (2015) 11:e1004642. doi:10.1371/journal.ppat.1004642.
115. McMaster SR, Gabbard JD, Koutsonanos DG, Compans RW, Tripp RA, Tompkins SM, et al. Memory T cells generated by prior exposure to influenza cross react with the novel H7N9 influenza virus and confer protective heterosubtypic immunity. PLoS One (2015) 10:e0115725. doi:10.1371/journal.pone.0115725.
116. Hillaire ML, Vogelzang-van Trierum SE, Kreijtz JH, de MG, Fouchier RA, Osterhaus AD, et al. Human T-cells directed to seasonal influenza A virus cross-react with 2009 pandemic influenza A (H1N1) and swine-origin triple-reassortant H3N2 influenza viruses. J Gen Virol (2013) 94:583-92. doi:10.1099/vir.0.048652-0.
117. Tu W, Mao H, Zheng J, Liu Y, Chiu SS, Qin G, et al. Cytotoxic T lymphocytes established by seasonal human influenza cross-react against 2009 pandemic H1N1 influenza virus. J Virol (2010) 84:6527-35. doi:10.1128/JVI.00519-10.
118. Gras S, Kedzierski L, Valkenburg SA, Laurie K, Liu YC, Denholm JT, et al. Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses. Proc Natl Acad Sci U S A (2010) 107:12599-604. doi:10.1073/pnas.1007270107.
119. Kreijtz JH, de MG, van Baalen CA, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. Cross-recognition of avian H5N1 influenza virus by human cytotoxic T-lymphocyte populations directed to human influenza A virus. J Virol (2008) 82:5161-6. doi:10.1128/JVI.02694-07.
120. van de Sandt CE, Kreijtz JH, de MG, Geelhoed-Mieras MM, Hillaire ML, Vogelzang-van Trierum SE, et al. Human cytotoxic T lymphocytes directed to seasonal influenza A viruses cross-react with the newly emerging H7N9 virus. J Virol (2014) 88:1684-93. doi:10.1128/JVI.02843-13.
121. Quinones-Parra S, Grant E, Loh L, Nguyen TH, Campbell KA, Tong SY, et al. Preexisting CD8+ T-cell immunity to the H7N9 influenza A virus varies across ethnicities. Proc Natl Acad Sci U S A (2014) 111:1049-54. doi:10.1073/pnas.1322229111.
122. McMichael AJ, Gotch FM, Noble GR, Beare PA. Cytotoxic T-cell immunity to influenza. N Engl J Med (1983) 309:13-7. doi:10.1056/NEJM198307073090103.
123. Sridhar S, Begom S, Bermingham A, Hoschler K, Adamson W, Carman W, et al. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat Med (2013) 19:1305-12. doi:10.1038/nm.3350.
124. Wang Z, Wan Y, Qiu C, Quinones-Parra S, Zhu Z, Loh L, et al. Recovery from severe H7N9 disease is associated with diverse response mechanisms dominated by CD8(+) T cells. Nat Commun (2015) 6:6833. doi:10.1038/ncomms7833.