Impact of distinct poxvirus infections on the specificities and functionalities of CD4+ T cell responses

Journal of Virology

Volumn 88, Issue 17, 2014, Pages 10078-10091

  Siciliano, Nicholas A ^a   Hersperger, Adam R ^a,d   Lacuanan, Aimee M ^a   Xu, Ren Huan ^b   Sidney, John ^c   Sette, Alessandro ^c   Sigal, Luis J ^b   Eisenlohr, Laurence C ^a  

^a THOMAS JEFFERSON UNIVERSITY   (United States)

^b FOX CHASE CANCER CENTER   (United States)

^c LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY   (United States)

^d ALBRIGHT COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; EPITOPE;

ANIMAL; BIOSYNTHESIS; C57BL MOUSE; CD4+ T LYMPHOCYTE; DISEASE MODEL; ECTROMELIA VIRUS; FEMALE; IMMUNOLOGICAL MEMORY; IMMUNOLOGY; POXVIRUS INFECTION; T LYMPHOCYTE SUBPOPULATION; VACCINIA VIRUS; VIROLOGY;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CYTOKINES; DISEASE MODELS, ANIMAL; ECTROMELIA VIRUS; EPITOPES; FEMALE; IMMUNOLOGIC MEMORY; MICE, INBRED C57BL; POXVIRIDAE INFECTIONS; T-LYMPHOCYTE SUBSETS; VACCINIA VIRUS;

EID: 84921956716     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.01150-14     Document Type: Article

References (113)

1. Janssen EM, Lemmens EE, Wolfe T, Christen U, von Herrath MG, Schoenberger SP. 2003. CD4+T cells are required for secondary expansion and memory in CD8+ T lymphocytes. Nature 421:852-856. http://dx.doi.org/10.1038/nature01441.
2. Nakanishi Y, Lu B, Gerard C, Iwasaki A. 2009. CD8(+) T lymphocyte mobilization to virus-infected tissue requires CD4(+) T-cell help. Nature 462:510-513. http://dx.doi.org/10.1038/nature08511.
3. Yin L, Calvo-Calle JM, Cruz J, Newman FK, Frey SE, Ennis FA, Stern LJ. 2013. CD4+ T cells provide intermolecular help to generate robust antibody responses in vaccinia virus-vaccinated humans. J. Immunol. 190:6023-6033. http://dx.doi.org/10.4049/jimmunol.1202523.
4. Crotty S, Kersh EN, Cannons J, Schwartzberg PL, Ahmed R. 2003. SAP is required for generating long-term humoral immunity. Nature 421: 282-287. http://dx.doi.org/10.1038/nature01318.
5. Darrah PA, Patel DT, De Luca PM, Lindsay RW, Davey DF, Flynn BJ, Hoff ST, Andersen P, Reed SG, Morris SL, Roederer M, Seder RA. 2007. Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat. Med. 13:843-850. http://dx.doi.org/10.1038/nm1592.
6. Zhu J, Paul WE. 2008. CD4 T cells: fates, functions, and faults. Blood 112:1557-1569. http://dx.doi.org/10.1182/blood-2008-05-078154.
7. Wan YY, Flavell RA. 2009. How diverse-CD4 effector T cells and their functions. J. Mol. Cell Biol. 1:20-36. http://dx.doi.org/10.1093/jmcb/mjp001.
8. Soghoian DZ, Jessen H, Flanders M, Sierra-Davidson K, Cutler S, Pertel T, Ranasinghe S, Lindqvist M, Davis I, Lane K, Rychert J, Rosenberg ES, Piechocka-Trocha A, Brass AL, Brenchley JM, Walker BD, Streeck H. 2012. HIV-specific cytolytic CD4 T cell responses during acute HIV infection predict disease outcome. Sci. Transl. Med. 4:123ra25. http://dx.doi.org/10.1126/scitranslmed.3003165.
9. Fang M, Siciliano NA, Hersperger AR, Roscoe F, Hu A, Ma X, Shamsedeen AR, Eisenlohr LC, Sigal LJ. 2012. Perforin-dependent CD4+ T-cell cytotoxicity contributes to control a murine poxvirus in-fection. Proc. Natl. Acad. Sci. U. S. A. 109:9983-9988. http://dx.doi.org/10.1073/pnas.1202143109.
10. Mahy BW, Almond JW, Berns KI, Chanock RM, Lvov DK, Pettersson RF, Schatzmayr HG, Fenner F. 1993. The remaining stocks of smallpox virus should be destroyed. Science 262:1223-1224. http://dx.doi.org/10.1126/science.8235651.
11. Anderson PD, Bokor G. 2012. Bioterrorism: pathogens as weapons. J. Pharm. Pract. 25:521-529. http://dx.doi.org/10.1177/0897190012456366.
12. Folio LR, Yao EF. 2007. US military smallpox vaccination program: occupational impact of immunizations on aircrew in Air Mobility Command, US Air Force. J. Am. Osteopath. Assoc. 107:547-553.
13. Whitby M, Street AC, Ruff TA, Fenner F. 2002. Biological agents as weapons 1: smallpox and botulism. Med. J. Aust. 176:431-433.
14. Esteban DJ, Buller RM. 2005. Ectromelia virus: the causative agent of mousepox. J. Gen. Virol. 86:2645-2659. http://dx.doi.org/10.1099/vir.0.81090-0.
15. Hersperger AR, Siciliano NA, Eisenlohr LC. 2012. Comparable polyfunctionality of ectromelia virus-and vaccinia virus-specific murine T cells despite markedly different in vivo replication and pathogenicity. J. Virol. 86:7298-7309. http://dx.doi.org/10.1128/JVI.00038-12.
16. Tscharke DC, Smith GL. 1999. A model for vaccinia virus pathogenesis and immunity based on intradermal injection of mouse ear pinnae. J. Gen. Virol. 80(Pt 10):2751-2755.
17. Jenkins MK, Khoruts A, Ingulli E, Mueller DL, McSorley SJ, Reinhardt RL, Itano A, Pape KA. 2001. In vivo activation of antigen-specific CD4 T cells. Annu. Rev. Immunol. 19:23-45. http://dx.doi.org/10.1146/annurev.immunol.19.1.23.
18. Tao X, Constant S, Jorritsma P, Bottomly K. 1997. Strength of TCR signal determines the costimulatory requirements for Th1 and Th2 CD4+ T cell differentiation. J. Immunol. 159:5956-5963.
19. Steinman RM, Hawiger D, Nussenzweig MC. 2003. Tolerogenic dendritic cells. Annu. Rev. Immunol. 21:685-711. http://dx.doi.org/10.1146/annurev.immunol.21.120601.141040.
20. Iwasaki A, Medzhitov R. 2004. Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5:987-995. http://dx.doi.org/10.1038/ni1112.
21. Zhu J, Yamane H, Paul WE. 2010. Differentiation of effector CD4 T cell populations. Annu. Rev. Immunol. 28:445-489. http://dx.doi.org/10.1146/annurev-immunol-030409-101212.
22. Khan S, van den Broek M, Schwarz K, de Giuli R, Diener PA, Groettrup M. 2001. Immunoproteasomes largely replace constitutive proteasomes during an antiviral and antibacterial immune response in the liver. J. Immunol. 167:6859-6868. http://dx.doi.org/10.4049/jimmunol.167.12.6859.
23. Smith VP, Alcami A. 2000. Expression of secreted cytokine and chemokine inhibitors by ectromelia virus. J. Virol. 74:8460-8471. http://dx.doi.org/10.1128/JVI.74.18.8460-8471.2000.
24. Alcami A, Smith GL. 1992. A soluble receptor for interleukin-1 beta encoded by vaccinia virus: a novel mechanism of virus modulation of the host response to infection. Cell 71:153-167. http://dx.doi.org/10.1016/0092-8674(92)90274-G.
25. Alcami A, Smith GL. 1995. Vaccinia, cowpox, and camelpox viruses encode soluble gamma interferon receptors with novel broad species specificity. J. Virol. 69:4633-4639.
26. Alcami A, Symons JA, Smith GL. 2000. The vaccinia virus soluble alpha/beta interferon (IFN) receptor binds to the cell surface and protects cells from the antiviral effects of IFN. J. Virol. 74:11230-11239. http://dx.doi.org/10.1128/JVI.74.23.11230-11239.2000.
27. Spriggs MK, Hruby DE, Maliszewski CR, Pickup DJ, Sims JE, Buller RM, VanSlyke J. 1992. Vaccinia and cowpox viruses encode a novel secreted interleukin-1-binding protein. Cell 71:145-152. http://dx.doi.org/10.1016/0092-8674(92)90273-F.
28. Born TL, Morrison LA, Esteban DJ, VandenBos T, Thebeau LG, Chen N, Spriggs MK, Sims JE, Buller RM. 2000. A poxvirus protein that binds to and inactivates IL-18, and inhibits NK cell response. J. Immunol. 164:3246-3254. http://dx.doi.org/10.4049/jimmunol.164.6.3246.
29. Bowie A, Kiss-Toth E, Symons JA, Smith GL, Dower SK, O'Neill LA. 2000. A46R and A52R from vaccinia virus are antagonists of host IL-1 and toll-like receptor signaling. Proc. Natl. Acad. Sci. U. S. A. 97:10162-10167. http://dx.doi.org/10.1073/pnas.160027697.
30. Loparev VN, Parsons JM, Knight JC, Panus JF, Ray CA, Buller RM, Pickup DJ, Esposito JJ. 1998. A third distinct tumor necrosis factor receptor of orthopoxviruses. Proc. Natl. Acad. Sci. U. S. A. 95:3786-3791. http://dx.doi.org/10.1073/pnas.95.7.3786.
31. Samuelsson C, Hausmann J, Lauterbach H, Schmidt M, Akira S, Wagner H, Chaplin P, Suter M, O'Keeffe M, Hochrein H. 2008. Survival of lethal poxvirus infection in mice depends on TLR9, and therapeutic vaccination provides protection. J. Clin. Invest. 118:1776-1784. http://dx.doi.org/10.1172/JCI33940.
32. Xu RH, Cohen M, Tang Y, Lazear E, Whitbeck JC, Eisenberg RJ, Cohen GH, Sigal LJ. 2008. The orthopoxvirus type I IFN binding protein is essential for virulence and an effective target for vaccination. J. Exp. Med. 205:981-992. http://dx.doi.org/10.1084/jem.20071854.
33. Rubio D, Xu RH, Remakus S, Krouse TE, Truckenmiller ME, Thapa RJ, Balachandran S, Alcami A, Norbury CC, Sigal LJ. 2013. Crosstalk between the type 1 interferon and nuclear factor kappa B pathways confers resistance to a lethal virus infection. Cell Host Microbe 13:701-710. http://dx.doi.org/10.1016/j.chom.2013.04.015.
34. Moutaftsi M, Bui HH, Peters B, Sidney J, Salek-Ardakani S, Oseroff C, Pasquetto V, Crotty S, Croft M, Lefkowitz EJ, Grey H, Sette A. 2007. Vaccinia virus-specific CD4+ T cell responses target a set of antigens largely distinct from those targeted by CD8+ T cell responses. J. Immunol. 178:6814-6820. http://dx.doi.org/10.4049/jimmunol.178.11.6814.
35. Siciliano NA, Skinner JA, Yuk MH. 2006. Bordetella bronchiseptica modulates macrophage phenotype leading to the inhibition of CD4+T cell proliferation and the initiation of a Th17 immune response. J. Immunol. 177: 7131-7138. http://dx.doi.org/10.4049/jimmunol.177.10.7131.
36. Chen N, Danila MI, Feng Z, Buller RM, Wang C, Han X, Lefkowitz EJ, Upton C. 2003. The genomic sequence of ectromelia virus, the causative agent of mousepox. Virology 317:165-186. http://dx.doi.org/10.1016/S0042-6822(03)00520-8.
37. O'Gorman WE, Sampath P, Simonds EF, Sikorski R, O'Malley M, Krutzik PO, Chen H, Panchanathan V, Chaudhri G, Karupiah G, Lewis DB, Thorne SH, Nolan GP. 2010. Alternate mechanisms of initial pattern recognition drive differential immune responses to related poxviruses. Cell Host Microbe 8:174-185. http://dx.doi.org/10.1016/j.chom.2010.07.008.
38. Marchal J. 1930. Infectious ectromelia: a hitherto undescribed virus disease of mice. J. Pathol. Bacteriol. 33:713-728. http://dx.doi.org/10.1002/path.1700330317.
39. Gubser C, Hue S, Kellam P, Smith GL. 2004. Poxvirus genomes: a phylogenetic analysis. J. Gen. Virol. 85:105-117. http://dx.doi.org/10.1099/vir.0.19565-0.
40. Fenner F. 1981. Mousepox (infectious ectromelia): past, present, and future. Lab. Anim. Sci. 31:553-559.
41. Roberts JA. 1962. Histopathogenesis of mousepox. II. Cutaneous infection. Br. J. Exp. Pathol. 43:462-468.
42. Fenner F. 1947. Studies in infectious ectromelia in mice; natural transmission; the portal of entry of the virus. Aust. J. Exp. Biol. Med. Sci. 25:275-282. http://dx.doi.org/10.1038/icb.1947.39.
43. Sakala IG, Chaudhri G, Buller RM, Nuara AA, Bai H, Chen N, Karupiah G. 2007. Poxvirus-encoded gamma interferon binding protein dampens the host immune response to infection. J. Virol. 81:3346-3353. http://dx.doi.org/10.1128/JVI.01927-06.
44. Karupiah G. 1998. Type 1 and type 2 cytokines in antiviral defense. Vet. Immunol. Immunopathol. 63:105-109. http://dx.doi.org/10.1016/S0165-2427(98)00086-5.
45. Isaacs A, Lindenmann J. 1957. Virus interference. I. The interferon. Proc. R. Soc. Lond. B Biol. Sci. 147:258-267. http://dx.doi.org/10.1098/rspb.1957.0048.
46. D'Souza WN, Schluns KS, Masopust D, Lefrancois L. 2002. Essential role for IL-2 in the regulation of antiviral extralymphoid CD8 T cell responses. J. Immunol. 168:5566-5572. http://dx.doi.org/10.4049/jimmunol.168.11.5566.
47. Seo SH, Webster RG. 2002. Tumor necrosis factor alpha exerts powerful anti-influenza virus effects in lung epithelial cells. J. Virol. 76:1071-1076. http://dx.doi.org/10.1128/JVI.76.3.1071-1076.2002.
48. Ruby J, Bluethmann H, Peschon JJ. 1997. Antiviral activity of tumor necrosis factor (TNF) is mediated via p55 and p75 TNF receptors. J. Exp. Med. 186:1591-1596. http://dx.doi.org/10.1084/jem.186.9.1591.
49. Chaudhri G, Panchanathan V, Buller RM, van den Eertwegh AJ, Claassen E, Zhou J, de Chazal R, Laman JD, Karupiah G. 2004. Polarized type 1 cytokine response and cell-mediated immunity determine genetic resistance to mousepox. Proc. Natl. Acad. Sci. U. S. A. 101:9057-9062. http://dx.doi.org/10.1073/pnas.0402949101.
50. Betts MR, Brenchley JM, Price DA, De Rosa SC, Douek DC, Roederer M, Koup RA. 2003. Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation. J. Immunol. Methods 281:65-78. http://dx.doi.org/10.1016/S0022-1759(03)00265-5.
51. Fenner F. 1989. Risks and benefits of vaccinia vaccine use in the worldwide smallpox eradication campaign. Res. Virol. 140:465-466. http://dx.doi.org/10.1016/S0923-2516(89)80126-8.
52. Hammarlund E, Lewis MW, Hansen SG, Strelow LI, Nelson JA, Sexton GJ, Hanifin JM, Slifka MK. 2003. Duration of antiviral immunity after smallpox vaccination. Nat. Med. 9:1131-1137. http://dx.doi.org/10.1038/nm917.
53. Casazza JP, Betts MR, Price DA, Precopio ML, Ruff LE, Brenchley JM, Hill BJ, Roederer M, Douek DC, Koup RA. 2006. Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation. J. Exp. Med. 203:2865-2877. http://dx.doi.org/10.1084/jem.20052246.
54. Casazza JP, Brenchley JM, Hill BJ, Ayana R, Ambrozak D, Roederer M, Douek DC, Betts MR, Koup RA. 2009. Autocrine production of beta-chemokines protects CMV-Specific CD4 T cells from HIV infection. PLoS Pathog. 5:e1000646. http://dx.doi.org/10.1371/journal.ppat.1000646.
55. Hersperger AR, Pereyra F, Nason M, Demers K, Sheth P, Shin LY, Kovacs CM, Rodriguez B, Sieg SF, Teixeira-Johnson L, Gudonis D, Goepfert PA, Lederman MM, Frank I, Makedonas G, Kaul R, Walker BD, Betts MR. 2010. Perforin expression directly ex vivo by HIV-specific CD8 T-cells is a correlate of HIV elite control. PLoS Pathog. 6:e1000917. http://dx.doi.org/10.1371/journal.ppat.1000917.
56. Moutaftsi M, Peters B, Pasquetto V, Tscharke DC, Sidney J, Bui HH, Grey H, Sette A. 2006. A consensus epitope prediction approach identifies the breadth of murine T(CD8+)-cell responses to vaccinia virus. Nat. Biotechnol. 24:817-819. http://dx.doi.org/10.1038/nbt1215.
57. Bauer S, Bathke B, Lauterbach H, Patzold J, Kassub R, Luber CA, Schlatter B, Hamm S, Chaplin P, Suter M, Hochrein H. 2010. A major role for TLR8 in the recognition of vaccinia viral DNA by murine pDC? Proc. Natl. Acad. Sci. U. S. A. 107:E139. http://dx.doi.org/10.1073/pnas.1008626107. (Reply, 107:E140, http://dx.doi.org/10.1073/pnas.1009858107.)
58. Symons JA, Adams E, Tscharke DC, Reading PC, Waldmann H, Smith GL. 2002. The vaccinia virus C12L protein inhibits mouse IL-18 and promotes virus virulence in the murine intranasal model. J. Gen. Virol. 83:2833-2844.
59. Moutaftsi M, Salek-Ardakani S, Croft M, Peters B, Sidney J, Grey H, Sette A. 2009. Correlates of protection efficacy induced by vaccinia virus-specific CD8+ T-cell epitopes in the murine intranasal challenge model. Eur. J. Immunol. 39:717-722. http://dx.doi.org/10.1002/eji.200838815.
60. Pepper M, Linehan JL, Pagan AJ, Zell T, Dileepan T, Cleary PP, Jenkins MK. 2010. Different routes of bacterial infection induce longlived TH1 memory cells and short-lived TH17 cells. Nat. Immunol. 11: 83-89. http://dx.doi.org/10.1038/ni.1826.
61. Kleindienst P, Brocker T. 2005. Concerted antigen presentation by dendritic cells and B cells is necessary for optimal CD4 T-cell immunity in vivo. Immunology 115:556-564. http://dx.doi.org/10.1111/j.1365-2567.2005.02196.x.
62. Spohr de Faundez I, Gierynska M, Niemialtowski MG, Malicka E, Popis A. 1995. Ectromelia virus establishes a persistent infection in spleen dendritic cells and macrophages of BALB/c mice following the acute disease. Adv. Exp. Med. Biol. 378:257-261. http://dx.doi.org/10.1007/978-1-4615-1971-3_57.
63. Briody BA. 1959. Response of mice to ectromelia and vaccinia viruses. Bacteriol. Rev. 23:61-95.
64. Fenner F. 1948. The pathogenesis of the acute exanthems; an interpretation based on experimental investigations with mousepox; infectious ectromelia of mice. Lancet ii:915-920.
65. Fenner F. 1949. Mouse-pox; infectious ectromelia of mice; a review. J. Immunol. 63:341-373.
66. Harrington LE, van der Most R, Whitton JL, Ahmed R. 2002. Recombinant vaccinia virus-induced T-cell immunity: quantitation of the response to the virus vector and the foreign epitope. J. Virol. 76:3329-3337. http://dx.doi.org/10.1128/JVI.76.7.3329-3337.2002.
67. Mahalingam S, Foster PS, Lobigs M, Farber JM, Karupiah G. 2000. Interferon-inducible chemokines and immunity to poxvirus infections. Immunol. Rev. 177:127-133. http://dx.doi.org/10.1034/j.1600-065X.2000.17720.x.
68. Delvig AA, Lee JJ, Chrzanowska-Lightowlers ZM, Robinson JH. 2002. TGF-beta1 and IFN-gamma cross-regulate antigen presentation to CD4 T cells by macrophages. J. Leukoc. Biol. 72:163-166.
69. Collins T, Korman AJ, Wake CT, Boss JM, Kappes DJ, Fiers W, Ault KA, Gimbrone MA, Jr, Strominger JL, Pober JS. 1984. Immune interferon activates multiple class II major histocompatibility complex genes and the associated invariant chain gene in human endothelial cells and dermal fibroblasts. Proc. Natl. Acad. Sci. U. S. A. 81:4917-4921. http://dx.doi.org/10.1073/pnas.81.15.4917.
70. Hastings KT. 2013. GILT: shaping the MHC class II-restricted peptidome and CD4 T cell-mediated immunity. Front. Immunol. 4:429. http://dx.doi.org/10.3389/fimmu.2013.00429.
71. Li P, Gregg JL, Wang N, Zhou D, O'Donnell P, Blum JS, Crotzer VL. 2005. Compartmentalization of class II antigen presentation: contribution of cytoplasmic and endosomal processing. Immunol. Rev. 207:206-217. http://dx.doi.org/10.1111/j.0105-2896.2005.00297.x.
72. Steimle V, Siegrist CA, Mottet A, Lisowska-Grospierre B, Mach B. 1994. Regulation of MHC class II expression by interferon-gamma mediated by the transactivator gene CIITA. Science 265:106-109. http://dx.doi.org/10.1126/science.8016643.
73. Oseroff C, Kos F, Bui HH, Peters B, Pasquetto V, Glenn J, Palmore T, Sidney J, Tscharke DC, Bennink JR, Southwood S, Grey HM, Yewdell JW, Sette A. 2005. HLA class I-restricted responses to vaccinia recognize a broad array of proteins mainly involved in virulence and viral gene regulation. Proc. Natl. Acad. Sci. U. S. A. 102:13980-13985. http://dx.doi.org/10.1073/pnas.0506768102.
74. Symons JA, Tscharke DC, Price N, Smith GL. 2002. A study of the vaccinia virus interferon-gamma receptor and its contribution to virus virulence. J. Gen. Virol. 83:1953-1964.
75. Igyarto BZ, Kaplan DH. 2013. Antigen presentation by Langerhans cells. Curr. Opin. Immunol. 25:115-119. http://dx.doi.org/10.1016/j.coi.2012.11.007.
76. Duraes FV, Thelemann C, Sarter K, Acha-Orbea H, Hugues S, Reith W. 2013. Role of major histocompatibility complex class II expression by non-hematopoietic cells in autoimmune and inflammatory disorders: facts and fiction. Tissue Antigens 82:1-15. http://dx.doi.org/10.1111/tan.12136.
77. Harari A, Vallelian F, Meylan PR, Pantaleo G. 2005. Functional heterogeneity of memory CD4 T cell responses in different conditions of antigen exposure and persistence. J. Immunol. 174:1037-1045. http://dx.doi.org/10.4049/jimmunol.174.2.1037.
78. Harari A, Vallelian F, Pantaleo G. 2004. Phenotypic heterogeneity of antigen-specific CD4 T cells under different conditions of antigen persistence and antigen load. Eur. J. Immunol. 34:3525-3533. http://dx.doi.org/10.1002/eji.200425324.
79. Shortman K, Liu YJ. 2002. Mouse and human dendritic cell subtypes. Nat. Rev. Immunol. 2:151-161. http://dx.doi.org/10.1038/nri746.
80. Appay V. 2004. The physiological role of cytotoxic CD4(+) T-cells: the holy grail? Clin. Exp. Immunol. 138:10-13. http://dx.doi.org/10.1111/j.1365-2249.2004.02605.x.
81. Brown DM. 2010. Cytolytic CD4 cells: direct mediators in infectious disease and malignancy. Cell. Immunol. 262:89-95. http://dx.doi.org/10.1016/j.cellimm.2010.02.008.
82. Pardo J, Galvez EM, Koskinen A, Simon MM, Lobigs M, Regner M, Mullbacher A. 2009. Caspase-dependent inhibition of mousepox replication by gzmB. PLoS One 4:e7512. http://dx.doi.org/10.1371/journal.pone.0007512.
83. Macen JL, Garner RS, Musy PY, Brooks MA, Turner PC, Moyer RW, McFadden G, Bleackley RC. 1996. Differential inhibition of the Fas-and granule-mediated cytolysis pathways by the orthopoxvirus cytokine response modifier A/SPI-2 and SPI-1 protein. Proc. Natl. Acad. Sci. U. S. A. 93:9108-9113. http://dx.doi.org/10.1073/pnas.93.17.9108.
84. Marcet-Palacios M, Duggan BL, Shostak I, Barry M, Geskes T, Wilkins JA, Yanagiya A, Sonenberg N, Bleackley RC. 2011. Granzyme B inhibits vaccinia virus production through proteolytic cleavage of eukaryotic initiation factor 4 gamma 3. PLoS Pathog. 7:e1002447. http://dx.doi.org/10.1371/journal.ppat.1002447.
85. Trapani JA, Sutton VR. 2003. Granzyme B: pro-apoptotic, antiviral and antitumor functions. Curr. Opin. Immunol. 15:533-543. http://dx.doi.org/10.1016/S0952-7915(03)00107-9.
86. Buzza MS, Zamurs L, Sun J, Bird CH, Smith AI, Trapani JA, Froelich CJ, Nice EC, Bird PI. 2005. Extracellular matrix remodeling by human granzyme B via cleavage of vitronectin, fibronectin, and laminin. J. Biol. Chem. 280:23549-23558. http://dx.doi.org/10.1074/jbc.M412001200.
87. Sallusto F, Geginat J, Lanzavecchia A. 2004. Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu. Rev. Immunol. 22:745-763. http://dx.doi.org/10.1146/annurev.immunol.22.012703.104702.
88. Williams MA, Ravkov EV, Bevan MJ. 2008. Rapid culling of the CD4+ T cell repertoire in the transition from effector to memory. Immunity 28:533-545. http://dx.doi.org/10.1016/j.immuni.2008.02.014.
89. Soghoian DZ, Streeck H. 2010. Cytolytic CD4(+) T cells in viral immunity. Exp. Rev. Vaccines 9:1453-1463. http://dx.doi.org/10.1586/erv.10.132.
90. Ye W, Young JD, Liu CC. 1996. Interleukin-15 induces the expression of mRNAs of cytolytic mediators and augments cytotoxic activities in primary murine lymphocytes. Cell. Immunol. 174:54-62. http://dx.doi.org/10.1006/cimm.1996.0293.
91. Picker LJ, Reed-Inderbitzin EF, Hagen SI, Edgar JB, Hansen SG, Legasse A, Planer S, Piatak M, Jr, Lifson JD, Maino VC, Axthelm MK, Villinger F. 2006. IL-15 induces CD4 effector memory T cell production and tissue emigration in nonhuman primates. J. Clin. Invest. 116:1514-1524. http://dx.doi.org/10.1172/JCI27564.
92. Fang M, Lanier LL, Sigal LJ. 2008. A role for NKG2D in NK cellmediated resistance to poxvirus disease. PLoS Pathog. 4:e30. http://dx.doi.org/10.1371/journal.ppat.0040030.
93. Kaech SM, Wherry EJ, Ahmed R. 2002. Effector and memory T-cell differentiation: implications for vaccine development. Nat. Rev. Immunol. 2:251-262. http://dx.doi.org/10.1038/nri778.
94. Han S, Asoyan A, Rabenstein H, Nakano N, Obst R. 2010. Role of antigen persistence and dose for CD4+ T-cell exhaustion and recovery. Proc. Natl. Acad. Sci. U. S. A. 107:20453-20458. http://dx.doi.org/10.1073/pnas.1008437107.
95. Barquet N, Domingo P. 1997. Smallpox: the triumph over the most terrible of the ministers of death. Ann. Intern. Med. 127:635-642. http://dx.doi.org/10.7326/0003-4819-127-8_Part_1-199710150-00010.
96. Baxby D. 1981. Jenner's smallpox vaccine: the riddle of the origin of vaccinia virus. Heinemann, London, England.
97. Behbehani AM. 1983. The smallpox story: life and death of an old disease. Microbiol. Rev. 47:455-509.
98. Bloch H. 1993. Edward Jenner (1749-1823). The history and effects of smallpox, inoculation, and vaccination. Am. J. Dis. Child. 147:772-774.
99. Dunn PM. 1996. Dr Edward Jenner (1749-1823) of Berkeley, and vaccination against smallpox. Arch. Dis. Child. Fetal Neonatal Ed. 74:F77-F78. http://dx.doi.org/10.1136/fn.74.1.F77.
100. Fenner F. 1977. The eradication of smallpox. Prog. Med. Virol. 23:1-21.
101. Fenner F. 1980. The global eradication of smallpox. Med. J. Aust. 1:455.
102. Fenner F. 1982. A successful eradication campaign. Global eradication of smallpox. Rev. Infect. Dis. 4:916-930.
103. Fenner F. 1984. Smallpox, "the most dreadful scourge of the human species." Its global spread and recent eradication. Med. J. Aust. 141:841-846.
104. Metzger W, Mordmueller BG. 2007. Vaccines for preventing smallpox. Cochrane Database Syst. Rev. 18:CD004913. http://dx.doi.org/10.1002/14651858.CD004913.pub2.
105. Willis NJ. 1997. Edward Jenner and the eradication of smallpox. Scott. Med. J. 42:118-121.
106. Lechner F, Wong DK, Dunbar PR, Chapman R, Chung RT, Dohrenwend P, Robbins G, Phillips R, Klenerman P, Walker BD. 2000. Analysis of successful immune responses in persons infected with hepatitis C virus. J. Exp. Med. 191:1499-1512. http://dx.doi.org/10.1084/jem.191.9.1499.
107. Lee BO, Rangel-Moreno J, Moyron-Quiroz JE, Hartson L, Makris M, Sprague F, Lund FE, Randall TD. 2005. CD4 T cell-independent antibody response promotes resolution of primary influenza infection and helps to prevent reinfection. J. Immunol. 175:5827-5838. http://dx.doi.org/10.4049/jimmunol.175.9.5827.
108. Shoukry NH, Cawthon AG, Walker CM. 2004. Cell-mediated immunity and the outcome of hepatitis C virus infection. Annu. Rev. Microbiol. 58:391-424. http://dx.doi.org/10.1146/annurev.micro.58.030603.123836.
109. Thomas PG, Keating R, Hulse-Post DJ, Doherty PC. 2006. Cellmediated protection in influenza infection. Emerg. Infect. Dis. 12:48-54. http://dx.doi.org/10.3201/eid1201.051237.
110. Wilkinson TM, Li CK, Chui CS, Huang AK, Perkins M, Liebner JC, Lambkin-Williams R, Gilbert A, Oxford J, Nicholas B, Staples KJ, Dong T, Douek DC, McMichael AJ, Xu XN. 2012. Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat. Med. 18:274-280. http://dx.doi.org/10.1038/nm.2612.
111. Zhou Y, Callendret B, Xu D, Brasky KM, Feng Z, Hensley LL, Guedj J, Perelson AS, Lemon SM, Lanford RE, Walker CM. 2012. Dominance of the CD4(+) T helper cell response during acute resolving hepatitis A virus infection. J. Exp. Med. 209:1481-1492. http://dx.doi.org/10.1084/jem.20111906.
112. Parker S, Siddiqui AM, Oberle C, Hembrador E, Lanier R, Painter G, Robertson A, Buller RM. 2009. Mousepox in the C57BL/6 strain provides an improved model for evaluating anti-poxvirus therapies. Virology 385:11-21. http://dx.doi.org/10.1016/j.virol.2008.11.015.
113. Boyle DB. 1989. How do other poxviruses fit in as potential vectored vaccine substrates for animal immunizations? Res. Virol. 140:483-485; discussion, 487-491.