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Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33136
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
-/- 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-
-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
-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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