The two faces of heterologous immunity: Protection or immunopathology

Journal of Leukocyte Biology

Volumn 95, Issue 3, 2014, Pages 405-416

  Sharma, Shalini ^a   Thomas, Paul G ^a  

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

Author keywords

Attrition; Bystander activation; Cross reactivity; Heterologous viral infections; Immunity; Immunodominance; T cell repertoire

Indexed keywords

VACCINE;

AUTOIMMUNITY; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CROSS REACTION; DISEASE MODEL; HAPLOTYPE; HETEROLOGOUS IMMUNITY; HISTOCOMPATIBILITY; HLA SYSTEM; HUMAN; IMMUNOMODULATION; IMMUNOPATHOLOGY; INFECTION PREVENTION; INNATE IMMUNITY; MIXED INFECTION; PRIORITY JOURNAL; REVIEW; SUPERINFECTION; T LYMPHOCYTE ACTIVATION; VACCINATION; ANIMAL; ATTRITION; BYSTANDER ACTIVATION; CROSS-REACTIVITY; HETEROLOGOUS VIRAL INFECTIONS; IMMUNITY; IMMUNODOMINANCE; IMMUNOLOGICAL MEMORY; IMMUNOLOGY; T CELL REPERTOIRE; VIRUS INFECTION;

ATTRITION; BYSTANDER ACTIVATION; CROSS-REACTIVITY; HETEROLOGOUS VIRAL INFECTIONS; IMMUNITY; IMMUNODOMINANCE; T CELL REPERTOIRE;

ANIMALS; HUMANS; IMMUNITY, HETEROLOGOUS; IMMUNOLOGIC MEMORY; VIRUS DISEASES;

EID: 84899478802     PISSN: 07415400     EISSN: 19383673     Source Type: Journal    
DOI: 10.1189/jlb.0713386     Document Type: Review

References (107)

1. Welsh, R. M., Che, J. W., Brehm, M. A., Selin, L. K. (2010) Heterologous immunity between viruses. Immunol. Rev. 235, 244-266.
2. Selin, L. K., Brehm, M. A. (2007) Frontiers in nephrology: heterologous immunity, T cell cross-reactivity, and alloreactivity. J. Am. Soc. Nephrol. 18, 2268-2277.
3. Mathurin, K. S., Martens, G. W., Kornfeld, H., Welsh, R. M. (2009) CD4 T-cell-mediated heterologous immunity between mycobacteria and poxviruses. J. Virol. 83, 3528-3539.
4. Rehermann, B., Shin, E. C. (2005) Private aspects of heterologous immunity. J. Exp. Med. 201, 667-670.
5. Clute, S. C., Naumov, Y. N., Watkin, L. B., Aslan, N., Sullivan, J. L., Thorley-Lawson, D. A., Luzuriaga, K., Welsh, R. M., Puzone, R., Celada, F., Selin, L. K. (2010) Broad cross-reactive TCR repertoires recognizing dissimilar Epstein-Barr and influenza A virus epitopes. J. Immunol. 185, 6753-6764.
6. Clute, S. C., Watkin, L. B., Cornberg, M., Naumov, Y. N., Sullivan, J. L., Luzuriaga, K., Welsh, R. M., Selin, L. K. (2005) Cross-reactive influenza virus-specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus-associated infectious mononucleosis. J. Clin. Invest. 115, 3602-3612.
7. Urbani, S., Amadei, B., Fisicaro, P., Pilli, M., Missale, G., Bertoletti, A., Ferrari, C. (2005) Heterologous T cell immunity in severe hepatitis C virus infection. J. Exp. Med. 201, 675-680.
8. Zivny, J., DeFronzo, M., Jarry, W., Jameson, J., Cruz, J., Ennis, F. A., Rothman, A. L. (1999) Partial agonist effect influences the CTL response to a heterologous dengue virus serotype. J. Immunol. 163, 2754-2760.
9. Welsh, R. M., Rothman, A. L. (2003) Dengue immune response: low affinity, high febrility. Nat. Med. 9, 820-822.
10. Mongkolsapaya, J., Dejnirattisai, W., Xu, X. N., Vasanawathana, S., Tangthawornchaikul, N., Chairunsri, A., Sawasdivorn, S., Duangchinda, T., Dong, T., Rowland-Jones, S., Yenchitsomanus, P. T., McMichael, A., Malasit, P., Screaton, G. (2003) Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever. Nat. Med. 9, 921-927.
11. Barton, E. S., White, D. W., Cathelyn, J. S., Brett-McClellan, K. A., Engle, M., Diamond, M. S., Miller, V. L., Virgin, H. W. (2007) Herpesvirus latency confers symbiotic protection from bacterial infection. Nature 447, 326-329.
12. Williams, A. E., Edwards, L., Humphreys, I. R., Snelgrove, R., Rae, A., Rappuoli, R., Hussell, T. (2004) Innate imprinting by the modified heat-labile toxin of Escherichia coli (LTK63) provides generic protection against lung infectious disease. J. Immunol. 173, 7435-7443.
13. Pawlowski, A., Jansson, M., Sköld, M., Rottenberg, M. E., Källenius, G. (2012) Tuberculosis and HIV co-infection. PLoS Pathog. 8, e1002464.
14. Page, K. R., Scott, A. L., Manabe, Y. C. (2006) The expanding realm of heterologous immunity: friend or foe? Cell. Microbiol. 8, 185-196.
15. Guidotti, L. G., Borrow, P., Hobbs, M. V., Matzke, B., Gresser, I., Oldstone, M. B., Chisari, F. V. (1996) Viral cross talk: intracellular inactivation of the hepatitis B virus during an unrelated viral infection of the liver. Proc. Natl. Acad. Sci. USA 93, 4589-4594.
16. De Jong, E. C., Vieira, P. L., Kalinski, P., Schuitemaker, J. H., Tanaka, Y., Wierenga, E. A., Yazdanbakhsh, M., Kapsenberg, M. L. (2002) Microbial compounds selectively induce Th1 cell-promoting or Th2 cellpromoting dendritic cells in vitro with diverse Th cell-polarizing signals. J. Immunol. 168, 1704-1709.
17. McGuirk, P., McCann, C., Mills, K. H. (2002) Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis. J. Exp. Med. 195, 221-231.
18. Smithey, M. J., Li, G., Venturi, V., Davenport, M. P., Nikolich-Žugich, J. (2012) Lifelong persistent viral infection alters the naive T cell pool, impairing CD8 T cell immunity in late life. J. Immunol. 189, 5356-5366.
19. Bevan, M. J. (2004) Helping the CD8(+) T-cell response. Nat. Rev. Immunol. 4, 595-602.
20. Selin, L. K., Varga, S. M., Wong, I. C., Welsh, R. M. (1998) Protective heterologous antiviral immunity and enhanced immunopathogenesis mediated by memory T cell populations. J. Exp. Med. 188, 1705-1715.
21. Sheth, P. M., Sunderji, S., Shin, L. Y., Rebbapragada, A., Huibner, S., Kimani, J., Macdonald, K. S., Ngugi, E., Bwayo, J. J., Moses, S., Kovacs, C., Loutfy, M., Kaul, R. (2008) Coinfection with herpes simplex virus type 2 is associated with reduced HIV-specific T cell responses and systemic immune activation. J. Infect. Dis. 197, 1394-1401.
22. Montes, M., Sanchez, C., Verdonck, K., Lake, J. E., Gonzalez, E., Lopez, G., Terashima, A., Nolan, T., Lewis, D. E., Gotuzzo, E., White, A. C. (2009) Regulatory T cell expansion in HTLV-1 and strongyloidiasis co-infection is associated with reduced IL-5 responses to Strongyloides stercoralis antigen. PLoS Negl. Trop. Dis. 3, e456.
23. Belkaid, Y., Rouse, B. T. (2005) Natural regulatory T cells in infectious disease. Nat. Immunol. 6, 353-360.
24. Suvas, S., Kumaraguru, U., Pack, C. D., Lee, S., Rouse, B. T. (2003) CD4+CD25+ T cells regulate virus-specific primary and memory CD8+ T cell responses. J. Exp. Med. 198, 889-901.
25. Toka, F. N., Suvas, S., Rouse, B. T. (2004) CD4+ CD25+ T cells regulate vaccine-generated primary and memory CD8+ T-cell responses against herpes simplex virus type 1. J. Virol. 78, 13082-13089.
26. Suvas, S., Azkur, A. K., Kim, B. S., Kumaraguru, U., Rouse, B. T. (2004) CD4+CD25+ regulatory T cells control the severity of viral immunoinflammatory lesions. J. Immunol. 172, 4123-4132.
27. Sharma, S., Sundararajan, A., Suryawanshi, A., Kumar, N., Veiga-Parga, T., Kuchroo, V. K., Thomas, P. G., Sangster, M. Y., Rouse, B. T. (2011) 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. USA 108, 19001-19006.
28. Sehrawat, S., Suryawanshi, A., Hirashima, M., Rouse, B. T. (2009) Role of Tim-3/galectin-9 inhibitory interaction in viral-induced immunopathology: shifting the balance toward regulators. J. Immunol. 182, 3191-3201.
29. Mason, D. (1998) A very high level of crossreactivity is an essential feature of the T-cell receptor. Immunol. Today 19, 395-404.
30. Yin, Y., Mariuzza, R. A. (2009) The multiple mechanisms of T cell receptor cross-reactivity. Immunity 31, 849-851.
31. Selin, L. K., Cornberg, M., Brehm, M. A., Kim, S. K., Calcagno, C., Ghersi, D., Puzone, R., Celada, F., Welsh, R. M. (2004) CD8 memory T cells: cross-reactivity and heterologous immunity. Semin. Immunol. 16, 335-347.
32. Selin, L. K., Welsh, R. M. (2004) Plasticity of T cell memory responses to viruses. Immunity 20, 5-16.
33. Welsh, R. M., Selin, L. K. (2002) No one is naive: the significance of heterologous T-cell immunity. Nat. Rev. Immunol. 2, 417-426.
34. Brehm, M. A., Pinto, A. K., Daniels, K. A., Schneck, J. P., Welsh, R. M., Selin, L. K. (2002) T cell immunodominance and maintenance of memory regulated by unexpectedly cross-reactive pathogens. Nat. Immunol. 3, 627-634.
35. Kim, S. K., Cornberg, M., Wang, X. Z., Chen, H. D., Selin, L. K., Welsh, R. M. (2005) Private specificities of CD8 T cell responses control patterns of heterologous immunity. J. Exp. Med. 201, 523-533.
36. Kim, S. K., Brehm, M. A., Welsh, R. M., Selin, L. K. (2002) Dynamics of memory T cell proliferation under conditions of heterologous immunity and bystander stimulation. J. Immunol. 169, 90-98.
37. Chen, H. D., Fraire, A. E., Joris, I., Brehm, M. A., Welsh, R. M., Selin, L. K. (2001) Memory CD8+ T cells in heterologous antiviral immunity and immunopathology in the lung. Nat. Immunol. 2, 1067-1076.
38. Walzl, G., Tafuro, S., Moss, P., Openshaw, P. J., Hussell, T. (2000) Influenza virus lung infection protects from respiratory syncytial virusinduced immunopathology. J. Exp. Med. 192, 1317-1326.
39. Chen, H. D., Fraire, A. E., Joris, I., Welsh, R. M., Selin, L. K. (2003) Specific history of heterologous virus infections determines anti-viral immunity and immunopathology in the lung. Am. J. Pathol. 163, 1341-1355.
40. Nikolich-Zugich, J., Slifka, M. K., Messaoudi, I. (2004) The many important facets of T-cell repertoire diversity. Nat. Rev. Immunol. 4, 123-132.
41. Davis, M. M., Bjorkman, P. J. (1988) T-cell antigen receptor genes and T-cell recognition. Nature 334, 395-402.
42. Naumov, Y. N., Naumova, E. N., Hogan, K. T., Selin, L. K., Gorski, J. (2003) A fractal clonotype distribution in the CD8+ memory T cell repertoire could optimize potential for immune responses. J. Immunol. 170, 3994-4001.
43. Pewe, L. L., Netland, J. M., Heard, S. B., Perlman, S. (2004) Very diverse CD8 T cell clonotypic responses after virus infections. J. Immunol. 172, 3151-3156.
44. Price, D. A., West, S. M., Betts, M. R., Ruff, L. E., Brenchley, J. M., Ambrozak, D. R., Edghill-Smith, Y., Kuroda, M. J., Bogdan, D., Kunstman, K., Letvin, N. L., Franchini, G., Wolinsky, S. M., Koup, R. A., Douek, D. C. (2004) T cell receptor recognition motifs govern immune escape patterns in acute SIV infection. Immunity 21, 793-803.
45. Meyer-Olson, D., Shoukry, N. H., Brady, K. W., Kim, H., Olson, D. P., Hartman, K., Shintani, A. K., Walker, C. M., Kalams, S. A. (2004) Limited T cell receptor diversity of HCV-specific T cell responses is associated with CTL escape. J. Exp. Med. 200, 307-319.
46. Borrow, P., Lewicki, H., Wei, X., Horwitz, M. S., Peffer, N., Meyers, H., Nelson, J. A., Gairin, J. E., Hahn, B. H., Oldstone, M. B., Shaw, G. M. (1997) Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat. Med. 3, 205-211.
47. Cornberg, M., Chen, A. T., Wilkinson, L. A., Brehm, M. A., Kim, S. K., Calcagno, C., Ghersi, D., Puzone, R., Celada, F., Welsh, R. M., Selin, L. K. (2006) Narrowed TCR repertoire and viral escape as a consequence of heterologous immunity. J. Clin. Invest. 116, 1443-1456.
48. Bitmansour, A. D., Waldrop, S. L., Pitcher, C. J., Khatamzas, E., Kern, F., Maino, V. C., Picker, L. J. (2001) Clonotypic structure of the human CD4+ memory T cell response to cytomegalovirus. J. Immunol. 167, 1151-1163.
49. Selin, L. K., Brehm, M. A., Naumov, Y. N., Cornberg, M., Kim, S. K., Clute, S. C., Welsh, R. M. (2006) Memory of mice and men: CD8+ Tcell cross-reactivity and heterologous immunity. Immunol. Rev. 211, 164-181.
50. Dong, T., Stewart-Jones, G., Chen, N., Easterbrook, P., Xu, X., Papagno, L., Appay, V., Weekes, M., Conlon, C., Spina, C., Little, S., Screaton, G., van der Merwe, A., Richman, D. D., McMichael, A. J., Jones, E. Y., Rowland-Jones, S. L. (2004) HIV-specific cytotoxic T cells from long-term survivors select a unique T cell receptor. J. Exp. Med. 200, 1547-1557.
51. Haanen, J. B., Wolkers, M. C., Kruisbeek, A. M., Schumacher, T. N. (1999) Selective expansion of cross-reactive CD8(+) memory T cells by viral variants. J. Exp. Med. 190, 1319-1328.
52. Crowe, S. R., Turner, S. J., Miller, S. C., Roberts, A. D., Rappolo, R. A., Doherty, P. C., Ely, K. H., Woodland, D. L. (2003) Differential antigen presentation regulates the changing patterns of CD8+ T cell immunodominance in primary and secondary influenza virus infections. J. Exp. Med. 198, 399-410.
53. Brehm, M. A., Selin, L. K., Welsh, R. M. (2004) CD8 T cell responses to viral infections in sequence. Cell. Microbiol. 6, 411-421.
54. Yewdell, J. W., Bennink, J. R. (1999) Immunodominance in major histocompatibility complex class I-restricted T lymphocyte responses. Annu. Rev. Immunol. 17, 51-88.
55. Cicin-Sain, L., Brien, J. D., Uhrlaub, J. L., Drabig, A., Marandu, T. F., Nikolich-Zugich, J. (2012) Cytomegalovirus infection impairs immune responses and accentuates T-cell pool changes observed in mice with aging. PLoS Pathog. 8, e1002849.
56. Wherry, E. J., Ahmed, R. (2004) Memory CD8 T-cell differentiation during viral infection. J. Virol. 78, 5535-5545.
57. Welsh, R. M., Selin, L. K. (2009) Attrition of memory CD8 T cells. Nature 459, E3-E4.
58. Vezys, V., Yates, A., Casey, K. A., Lanier, G., Ahmed, R., Antia, R., Masopust, D. (2009) Memory CD8 T-cell compartment grows in size with immunological experience. Nature 457, 196-199.
59. Huster, K. M., Stemberger, C., Gasteiger, G., Kastenmüller, W., Drexler, I., Busch, D. H. (2009) Cutting edge: memory CD8 T cell compartment grows in size with immunological experience but nevertheless can lose function. J. Immunol. 183, 6898-6902.
60. Jiang, J., Lau, L. L., Shen, H. (2003) Selective depletion of nonspecific T cells during the early stage of immune responses to infection. J. Immunol. 171, 4352-4358.
61. Selin, L. K., Lin, M. Y., Kraemer, K. A., Pardoll, D. M., Schneck, J. P., Varga, S. M., Santolucito, P. A., Pinto, A. K., Welsh, R. M. (1999) Attrition of T cell memory: selective loss of LCMV epitope-specific memory CD8 T cells following infections with heterologous viruses. Immunity 11, 733-742.
62. McNally, J. M., Zarozinski, C. C., Lin, M. Y., Brehm, M. A., Chen, H. D., Welsh, R. M. (2001) Attrition of bystander CD8 T cells during virus-induced T-cell and interferon responses. J. Virol. 75, 5965-5976.
63. Kim, S. K., Welsh, R. M. (2004) Comprehensive early and lasting loss of memory CD8 T cells and functional memory during acute and persistent viral infections. J. Immunol. 172, 3139-3150.
64. Smith, D. K., Dudani, R., Pedras-Vasconcelos, J. A., Chapdelaine, Y., van Faassen, H., Sad, S. (2002) Cross-reactive antigen is required to prevent erosion of established T cell memory and tumor immunity: a heterologous bacterial model of attrition. J. Immunol. 169, 1197-1206.
65. Bahl, K., Kim, S. K., Calcagno, C., Ghersi, D., Puzone, R., Celada, F., Selin, L. K., Welsh, R. M. (2006) IFN-induced attrition of CD8 T cells in the presence or absence of cognate antigen during the early stages of viral infections. J. Immunol. 176, 4284-4295.
66. Dudani, R., Murali-Krishna, K., Krishnan, L., Sad, S. (2008) IFN-γ induces the erosion of preexisting CD8 T cell memory during infection with a heterologous intracellular bacterium. J. Immunol. 181, 1700-1709.
67. Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., Ahmed, R. (2006) Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439, 682-687.
68. Lin, S. J., Peacock, C. D., Bahl, K., Welsh, R. M. (2007) Programmed death-1 (PD-1) defines a transient and dysfunctional oligoclonal T cell population in acute homeostatic proliferation. J. Exp. Med. 204, 2321-2333.
69. Yang, H. Y., Joris, I., Majno, G., Welsh, R. M. (1985) Necrosis of adipose tissue induced by sequential infections with unrelated viruses. Am. J. Pathol. 120, 173-177.
70. Nie, S., Lin, S. J., Kim, S. K., Welsh, R. M., Selin, L. K. (2010) Pathological features of heterologous immunity are regulated by the private specificities of the immune repertoire. Am. J. Pathol. 176, 2107-2112.
71. Wlodarczyk, M. F., Kraft, A. R., Chen, H. D., Kenney, L. L., Selin, L. K. (2013) Anti-IFN-γ and peptide-tolerization therapies inhibit acute lung injury induced by cross-reactive influenza A-specific memory T cells. J. Immunol. 190, 2736-2746.
72. Jamieson, A. M., Yu, S., Annicelli, C. H., Medzhitov, R. (2010) Influenza virus-induced glucocorticoids compromise innate host defense against a secondary bacterial infection. Cell Host Microbe 7, 103-114.
73. Onyeagocha, C., Hossain, M. S., Kumar, A., Jones, R. M., Roback, J., Gewirtz, A. T. (2009) Latent cytomegalovirus infection exacerbates experimental colitis. Am. J. Pathol. 175, 2034-2042.
74. Christen, U., Edelmann, K. H., McGavern, D. B., Wolfe, T., Coon, B., Teague, M. K., Miller, S. D., Oldstone, M. B., von Herrath, M. G. (2004) A viral epitope that mimics a self antigen can accelerate but not initiate autoimmune diabetes. J. Clin. Invest. 114, 1290-1298.
75. Evans, C. F., Horwitz, M. S., Hobbs, M. V., Oldstone, M. B. (1996) Viral infection of transgenic mice expressing a viral protein in oligodendrocytes leads to chronic central nervous system autoimmune disease. J. Exp. Med. 184, 2371-2384.
76. Mathew, A., Kurane, I., Green, S., Stephens, H. A., Vaughn, D. W., Kalayanarooj, S., Suntayakorn, S., Chandanayingyong, D., Ennis, F. A., Rothman, A. L. (1998) Predominance of HLA-restricted cytotoxic Tlymphocyte responses to serotype-cross-reactive epitopes on nonstructural proteins following natural secondary dengue virus infection. J. Virol. 72, 3999-4004.
77. Wedemeyer, H., Mizukoshi, E., Davis, A. R., Bennink, J. R., Rehermann, B. (2001) Cross-reactivity between hepatitis C virus and influenza A virus determinant-specific cytotoxic T cells. J. Virol. 75, 11392-11400.
78. Acierno, P. M., Newton, D. A., Brown, E. A., Maes, L. A., Baatz, J. E., Gattoni-Celli, S. (2003) Cross-reactivity between HLA-A2-restricted FLUM1: 58-66 and HIV p17 GAG:77-85 epitopes in HIV-infected and uninfected individuals. J. Transl. Med. 1, 3.
79. Nilges, K., Höhn, H., Pilch, H., Neukirch, C., Freitag, K., Talbot, P. J., Maeurer, M. J. (2003) Human papillomavirus type 16 E7 peptide-directed CD8+ T cells from patients with cervical cancer are cross-reactive with the coronavirus NS2 protein. J. Virol. 77, 5464-5474.
80. Duerkop, B. A., Hooper, L. V. (2013) Resident viruses and their interactions with the immune system. Nat. Immunol. 14, 654-659.
81. Welsh, R. M., Fujinami, R. S. (2007) Pathogenic epitopes, heterologous immunity and vaccine design. Nat. Rev. Microbiol. 5, 555-563.
82. Halstead, S. B. (2007) Dengue. Lancet 370, 1644-1652.
83. Van Leeuwen, E. M., Koning, J. J., Remmerswaal, E. B., van Baarle, D., van Lier, R. A., ten Berge, I. J. (2006) Differential usage of cellular niches by cytomegalovirus versus EBV-and influenza virus-specific CD8+ T cells. J. Immunol. 177, 4998-5005.
84. + T cell memory in humans. J. Exp. Med. 209, 471-478.
85. Zhang, J. Y., Zhang, Z., Jin, B., Zhang, S. Y., Zhou, C. B., Fu, J. L., Wang, F. S. (2008) Cutting edge: programmed death-1 up-regulation is involved in the attrition of cytomegalovirus-specific CD8+ T cells in acute self-limited hepatitis B virus infection. J. Immunol. 181, 3741-3744.
86. Hammarlund, E., Lewis, M. W., Hansen, S. G., Strelow, L. I., Nelson, J. A., Sexton, G. J., Hanifin, J. M., Slifka, M. K. (2003) Duration of antiviral immunity after smallpox vaccination. Nat. Med. 9, 1131-1137.
87. Kohlmeier, J. E., Cookenham, T., Roberts, A. D., Miller, S. C., Woodland, D. L. (2010) Type I interferons regulate cytolytic activity of memory CD8(+) T cells in the lung airways during respiratory virus challenge. Immunity 33, 96-105.
88. Marshall, H. D., Prince, A. L., Berg, L. J., Welsh, R. M. (2010) IFN-α β and self-MHC divert CD8 T cells into a distinct differentiation pathway characterized by rapid acquisition of effector functions. J. Immunol. 185, 1419-1428.
89. Doisne, J. M., Urrutia, A., Lacabaratz-Porret, C., Goujard, C., Meyer, L., Chaix, M. L., Sinet, M., Venet, A. (2004) CD8+ T cells specific for EBV, cytomegalovirus, and influenza virus are activated during primary HIV infection. J. Immunol. 173, 2410-2418.
90. Sandalova, E., Laccabue, D., Boni, C., Tan, A. T., Fink, K., Ooi, E. E., Chua, R., Shafaeddin Schreve, B., Ferrari, C., Bertoletti, A. (2010) Contribution of herpesvirus specific CD8 T cells to anti-viral T cell response in humans. PLoS Pathog. 6, e1001051.
91. Hansen, S. G., Powers, C. J., Richards, R., Ventura, A. B., Ford, J. C., Siess, D., Axthelm, M. K., Nelson, J. A., Jarvis, M. A., Picker, L. J., Früh, K. (2010) Evasion of CD8+ T cells is critical for superinfection by cytomegalovirus. Science 328, 102-106.
92. Yewdell, J. W. (2006) Confronting complexity: real-world immunodominance in antiviral CD8+ T cell responses. Immunity 25, 533-543.
93. Oseroff, C., Kos, F., Bui, H. H., Peters, B., Pasquetto, V., Glenn, J., Palmore, T., Sidney, J., Tscharke, D. C., Bennink, J. R., Southwood, S., Grey, H. M., Yewdell, J. W., 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. USA 102, 13980-13985.
94. Sylwester, A. W., Mitchell, B. L., Edgar, J. B., Taormina, C., Pelte, C., Ruchti, F., Sleath, P. R., Grabstein, K. H., Hosken, N. A., Kern, F., Nelson, J. A., Picker, L. J. (2005) Broadly targeted human cytomegalovirusspecific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J. Exp. Med. 202, 673-685.
95. Hosken, N., McGowan, P., Meier, A., Koelle, D. M., Sleath, P., Wagener, F., Elliott, M., Grabstein, K., Posavad, C., Corey, L. (2006) Diversity of the CD8+ T-cell response to herpes simplex virus type 2 proteins among persons with genital herpes. J. Virol. 80, 5509-5515.
96. Su, L. F., Kidd, B. A., Han, A., Kotzin, J. J., Davis, M. M. (2013) Virusspecific CD4(+) memory-phenotype T cells are abundant in unexposed adults. Immunity 38, 373-383.
97. Levy, P. Y., Fenollar, F., Stein, A., Borrione, F., Raoult, D. (2009) Finegoldia magna: a forgotten pathogen in prosthetic joint infection rediscovered by molecular biology. Clin. Infect. Dis. 49, 1244-1247.
98. Nie, S., Cornberg, M., Selin, L. K. (2009) Resistance to vaccinia virus is less dependent on TNF under conditions of heterologous immunity. J. Immunol. 183, 6554-6560.
99. Wang, G. C., Dash, P., McCullers, J. A., Doherty, P. C., Thomas, P. G. (2012) T cell receptor αβ diversity inversely correlates with pathogenspecific antibody levels in human cytomegalovirus infection. Sci. Transl. Med. 4, 128ra42.
100. Beswick, M., Pachnio, A., Lauder, S. N., Sweet, C., Moss, P. A. (2013) Antiviral therapy can reverse the development of immune senescence in elderly mice with latent cytomegalovirus infection. J. Virol. 87, 779-789.
101. Li, Y., Li, X. C., Zheng, X. X., Wells, A. D., Turka, L. A., Strom, T. B. (1999) Blocking both signal 1 and signal 2 of T-cell activation prevents apoptosis of alloreactive T cells and induction of peripheral allograft tolerance. Nat. Med. 5, 1298-1302.
102. Jones, T. R., Ha, J., Williams, M. A., Adams, A. B., Durham, M. M., Rees, P. A., Cowan, S. R., Pearson, T. C., Larsen, C. P. (2002) The role of the IL-2 pathway in costimulation blockade-resistant rejection of allografts. J. Immunol. 168, 1123-1130.
103. Demirci, G., Gao, W., Zheng, X. X., Malek, T. R., Strom, T. B., Li, X. C. (2002) On CD28/CD40 ligand costimulation, common γ-chain signals, and the alloimmune response. J. Immunol. 168, 4382-4390.
104. Adams, A. B., Williams, M. A., Jones, T. R., Shirasugi, N., Durham, M. M., Kaech, S. M., Wherry, E. J., Onami, T., Lanier, J. G., Kokko, K. E., Pearson, T. C., Ahmed, R., Larsen, C. P. (2003) Heterologous immunity provides a potent barrier to transplantation tolerance. J. Clin. Invest. 111, 1887-1895.
105. Singh, N. (2005) Interactions between viruses in transplant recipients. Clin. Infect. Dis. 40, 430-436.
106. Cornberg, M., Clute, S. C., Watkin, L. B., Saccoccio, F. M., Kim, S. K., Naumov, Y. N., Brehm, M. A., Aslan, N., Welsh, R. M., Selin, L. K. (2010) CD8 T cell cross-reactivity networks mediate heterologous immunity in human EBV and murine vaccinia virus infections. J. Immunol. 184, 2825-2838.
107. Benn, C. S., Netea, M. G., Selin, L. K., Aaby, P. (2013) A small jab-a big effect: nonspecific immunomodulation by vaccines. Trends Immunol. 34, 431-439.