Essential roles for CD8(+) T cells and gamma interferon in protection of mice against retrovirus-induced immunosuppression

It is known that both animal and human retroviruses typically cause immunos uppression in their respective hosts, but the mechanisms by which this occu rs are poorly understood. The present study uses Friend virus (FV) infectio ns of mice as a model to determine how major histocompatibility complex (MH C) genes influence immunosuppression. Previously, MHC-I genes were shown to influence antibody responses to potent antigenic challenges given during a cute FY infection. The mapping of an immune response to an MHC-I gene impli cated CD8(+) T cells in the mechanism, so we directly tested for their role by using in vivo CD8(+) T-cell depletions. Mice resistant to FV-induced im munosuppression became susceptible when they were depleted of CD8+ T cells. Resistance also required gamma interferon (IFN-gamma), as in vivo neutrali zation of IFN-gamma converted mice from a resistant to susceptible phenotyp e. On the other hand, susceptibility to FV-induced immunosuppression was de pendent on the immunosuppressive cytokine, interleukin-10 (IL-10), as antib ody responses were restored in susceptible mice when IL-10 function was blo cked in vivo. Thus, FV-induced immunosuppression of antibody responses invo lves complex mechanisms controlled at least in part by CD8(+) T cells.