CD4+ and CD8+ T cell interactions in IFN-gamma 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 beta2-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 vivo. Studies in IL-2-deficient mice demonstrated that this cytokine promoted IFN-gamma and IL-4 responses, and ex vivo 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.
Su
H C
HC
Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.
Cousens
L P
LP
Fast
L D
LD
Slifka
M K
MK
Bungiro
R D
RD
Ahmed
R
R
Biron
C A
CA
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002450:Cell Communication; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D000914:Antibodies, Viral; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma