Generation of antiviral major histocompatibility complex class I-restricted T cells in the absence of CD8 coreceptors.
The CD8 coreceptor is important for positive selection of major histocompatibility complex I (MHC-I)-restricted thymocytes and in the generation of pathogen-specific T cells. However, the requirement for CD8 in these processes may not be essential. We previously showed that mice lacking beta(2)-microglobulin are highly susceptible to tumors induced by mouse polyoma virus (PyV), but CD8-deficient mice are resistant to these tumors. In this study, we show that CD8-deficient mice also control persistent PyV infection as efficiently as wild-type mice and generate a substantial virus-specific, MHC-I-restricted, T-cell response. Infection with vesicular stomatitis virus (VSV), which is acutely cleared, also recruited antigen-specific, MHC-I-restricted T cells in CD8-deficient mice. Yet, unlike in VSV infection, the antiviral MHC-I-restricted T-cell response to PyV has a prolonged expansion phase, indicating a requirement for persistent infection in driving T-cell inflation in CD8-deficient mice. Finally, we show that the PyV-specific, MHC-I-restricted T cells in CD8-deficient mice, while maintained long term at near-wild-type levels, are short lived in vivo and have extremely narrow T-cell receptor repertoires. These findings provide a possible explanation for the resistance of CD8-deficient mice to PyV-induced tumors and have implications for the maintenance of virus-specific MHC-I-restricted T cells during persistent infection.
Andrews
Nicolas P
NP
Department of Pathology, Emory University School of Medicine, Woodruff Memorial Research Building, 101 Woodruff Circle, Atlanta, GA 30322, USA.
Pack
Christopher D
CD
Lukacher
Aron E
AE
D019264:Adoptive Transfer; D000818:Animals; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011120:Polyomavirus / Q000276:immunology*; D027601:Polyomavirus Infections / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D018353:Rhabdoviridae Infections / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000382:microbiology*; D013997:Time Factors; D018116:Vesiculovirus / Q000276:immunology*
D017252:CD3 Complex; D015704:CD4 Antigens; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma