Generation of antiviral MHC class I-restricted T cells in the absence of CD8 coreceptors

Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322

^* To whom correspondence should be addressed. Email: alukach{at}emory.edu.

	Abstract

The CD8 coreceptor is important for positive selection of 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 ₂-microglobulin are highly susceptible to tumors induced by mouse polyoma virus (PyV), but CD8-deficient mice are resistant. 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 an extremely narrow TCR repertoire. 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.