CD4+ and CD8+ T cell interactions in IFN-γ and IL-4 responses to viral infections:: Requirements for IL-2

Cytokine responses to lymphocytic choriomeningitis virus infections were evaluated, and CD8(+) T cell, CD4(+) T cell, and IL-2 contributions delineated, In immunocompetent mice, lymphocytic choriomeningitis virus induced both IFN-gamma and IL-4 as well as IL-2, Experiments in mice either beta(2)-microglobulin-deficient, lacking MHC class I molecules and CD8(+) T cells, or A beta(b)-deficient, lacking MHC class II molecules and CD4(+) T cells, demonstrated that mixtures of T cell responses were required for optimal ex vivo cytokine productions. Intracellular cytokine expression analyses of cells from immunocompetent and immunodeficient mice showed that CD8(+) T cells were predominant IFN-gamma producers, and that expansion of CD8(+) T cells primed to make IFN-gamma was independent of CD4(+) T cells in vive, Studies in IL-2-deficient mice demonstrated that this cytokine promoted IFN-gamma and IL-4 responses, and ex vive experiments showed that exogenous IL-2 was required to maintain high-level IFN-gamma production by in vivo-primed CD8(+) T cells, Conditions associated with cytokine decreases were accompanied by reduced detectable plasma Ab responses. The results indicate that, although IL-2-dependent CD8+ T cell proliferation does not require endogenous CD4(+) T cells, IL-2 production by the CD4(+) T cells may promote continued cytokine release from activated CD8(+) T cells. By defining these critical steps in cellular and cytokine interactions for shaping endogenous immune responses, the studies advance understanding of the unique conditions regulating CD8(+) T cell responses to viral challenges.