Altered Kinetics of CD4+T Cell Proliferation and Interferon-γ Production in the Absence of CD8+T Lymphocytes in Virus-Infected β2-Microglobulin-Deficient Mice

Abstract

CD8+T cells are the major mediators of cytotoxic T cell activity controlling viral infections in normal mice. CD8+T cells have also been implicated in regulating the activity of other immune cells. We have examined the possible regulatory role of CD8+T cells on CD4+T cells by comparing immune responses in mice expressing normal CD8+T cell responses and in CD8+T cell-deficient β2-microglobulin “knockout” mice. In normal mice, infection with lymphocytic choriomeningitis virus (LCMV) results in a biphasic T cell immune response. First, CD8+T cells proliferate and produce interferon-γ (IFN-γ), and then 2 to 4 days later CD4+T cells proliferate and produce IFN-γ. CD8+T cell activity is not detected during LCMV infection in β2-microglobulin-deficient mice. However, in β2-microglobulin-deficient mice the CD4+T cell expansion is exaggerated and occurs 2 days earlier than observed in normal mice. Furthermore, the CD4+T cells have substantial cytotoxic activity, which is not observed in the CD4+T cell population in normal mice. However, CD4+T cell IFN-γ production in β2-microglobulin-deficient mice lags behind the proliferative response, resulting in a relative delay in overall T cell IFN-γ production compared to normal mice. Taken together, these data suggest that CD8+T cell activation peaks at an earlier time point than CD4+T cell activation during the primary immune response to LCMV and that CD8+T cells may inhibit CD4+T cell proliferation and the development of CD4+T cell cytotoxic activity.