TY - JOUR
T1 - CD4+ and CD8+ T cell interactions in IFN-γ and IL-4 responses to viral infections
T2 - Requirements for IL-2
AU - Su, Helen C.
AU - Cousens, Leslie P.
AU - Fast, Loren D.
AU - Slifka, Mark K.
AU - Bungiro, Richard D.
AU - Ahmed, Rafi
AU - Biron, Christine A.
PY - 1998/5/15
Y1 - 1998/5/15
N2 - 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 choriomeningitls virus induced both IFN- γ, and IL-4 as well as IL-2. Experiments in mice either β2-microglobulin- deficient, lacking MHC class I molecules and CD8+ T cells, or Aβ(b)- deficient, lacking MHC class H 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-γ producers, and that expansion of CD8+ T cells primed to make IFN-γ was independent of CD4+ T cells in vivo. Studies in IL-2- deficient mice demonstrated that this cytokine promoted IFN-γ and IL-4 responses, and ex vivo experiments showed that exogenous IL-2 was required to maintain high-level IFN-γ 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.
AB - 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 choriomeningitls virus induced both IFN- γ, and IL-4 as well as IL-2. Experiments in mice either β2-microglobulin- deficient, lacking MHC class I molecules and CD8+ T cells, or Aβ(b)- deficient, lacking MHC class H 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-γ producers, and that expansion of CD8+ T cells primed to make IFN-γ was independent of CD4+ T cells in vivo. Studies in IL-2- deficient mice demonstrated that this cytokine promoted IFN-γ and IL-4 responses, and ex vivo experiments showed that exogenous IL-2 was required to maintain high-level IFN-γ 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.
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M3 - Article
C2 - 9590250
AN - SCOPUS:0032524968
SN - 0022-1767
VL - 160
SP - 5007
EP - 5017
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -