Altered kinetics of CD4+ T cell proliferation and interferon-gamma production in the absence of CD8+ T lymphocytes in virus-infected beta2-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 beta2-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 beta2-microglobulin-deficient mice. However, in beta2-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 beta2-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.
Department of Medicine, University of Wisconsin--Madison, 53706, USA.
A
A
Vikingsson
K
K
Pederson
D
D
Muller
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D008211:Lymphocyte Cooperation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000276:immunology*
D001613:beta 2-Microglobulin; D007371:Interferon-gamma