Altered kinetics of CD4(+) T cell proliferation and interferon-gamma production in the absence of CD8(+) T lymphocytes in virus-infected beta 2-microglobulin-deficient mice

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 beta 2-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-gamma (IFN-gamma), and then 2 to 4 days later CD4(+) T cells proliferate and produce IFN-gamma. CD8(+) T cell activity is not detected during LCMV infection in beta 2-microglobulin-deficient mice. However, in beta 2-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-gamma production in beta 2-microglobulin-deficient mice lags behind the proliferative response, resulting in a relative delay in overall T cell IFN-gamma 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. (C) 1996 Academic Press, Inc