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)
A. Vikingsson et al., 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), Cellular immunology, 173(2), 1996, pp. 261-268
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