Journal
JOURNAL OF IMMUNOLOGY
Volume 166, Issue 3, Pages 1675-1683Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.166.3.1675
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- NIAID NIH HHS [AI40114] Funding Source: Medline
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Coincident production of IL-2 and induction of high-affinity IL-2R upon TCR engagement has precluded a clear distinction for the biological outcome of signaling through TCR/costimulatory molecules vs the IL-2R, Using a novel transgenic mouse on the IL-2R beta (-/-) genetic background, this study has separated the relative outcome of signaling through the TCR and IL-2R, We show that stimulation through the TCR and CD28 or CD40 ligand directly leads to T cell activation and several rounds of proliferation in an IL-2-independent fashion. However, this stimulation is insufficient for extended T cell growth to multiple cytokines or differentiation into CTL or IFN-gamma -secreting effector T cells. IL-2 is required for these functions in part by regulation of cyclin D3 and granzyme B, Somewhat less efficiently, IL-4 stimulation of these transgenic T cells redundantly rescued many of these activities, These data demonstrate a fundamental requirement for IL-2 and perhaps other common gamma -chain-dependent cytokines to promote selective gene expression by Ag-activated T cells for their subsequent growth and differentiation into effector T lymphocytes.
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