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

Helen C. Su, Leslie P. Cousens, Loren D. Fast, Mark K. Slifka, Richard D. Bungiro, Rafi Ahmed, Christine A. Biron

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)5007-5017
Number of pages11
JournalJournal of Immunology
Issue number10
StatePublished - May 15 1998
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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