Broad programming by IL-2 receptor signaling for extended growth to multiple cytokines and functional maturation of antigen-activated T cells

T. R. Malek, A. Yu, P. Scibelli, M. G. Lichtenheld, E. K. Codias

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

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-2Rβ-/- 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-γ-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 γ-chain-dependent cytokines to promote selective gene expression by Ag-activated T cells for their subsequent growth and differentiation into effector T lymphocytes.

Original languageEnglish (US)
Pages (from-to)1675-1683
Number of pages9
JournalJournal of Immunology
Volume166
Issue number3
DOIs
StatePublished - Feb 1 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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