ALTERED KINETICS OF CD4(-CELL PROLIFERATION AND INTERFERON-GAMMA PRODUCTION IN THE ABSENCE OF CD8(+) T-LYMPHOCYTES IN VIRUS-INFECTED BETA-2-MICROGLOBULIN-DEFICIENT MICE() T)

CD8(+) T cells are the major mediators of cytotoxic T cell activity co ntrolling viral infections in normal mice. CD8(+) T cells have also be en implicated in regulating the activity of other immune cells. We hav e 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 choriomeni ngitis virus (LCMV) results in a biphasic T cell immune response. Firs t, CD8(+) T cells proliferate and produce interferon-gamma (IFN-gamma) , and then 2 to 4 days later CD4(+) T cells proliferate and produce IF N-gamma. CD8(+) T cell activity is not detected during LCMV infection in beta 2-microglobulin-deficient mice. However, in beta 2-microglobul in-deficient mice the CD4(+) T cell expansion is exaggerated and occur s 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 I FN-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, t hese data suggest that CD8(+) T cell activation peaks at an earlier ti me point than CD4(+) T cell activation during the primary immune respo nse to LCMV and that CD8(+) T cells may inhibit CD4(+) T cell prolifer ation and the development of CD4(+) T cell cytotoxic activity. (C) 199 6 Academic Press, Inc