OX40-mediated differentiation to effector function requires IL-2 receptor signaling but not CD28, CD40, IL-12Rβ2, or T-bet

Cortny A. Williams, Susan E. Murray, Andrew D. Weinberg, David C. Parker

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Ag-specific CD4 T cells transferred into unirradiated Ag-bearing recipients proliferate, but survival and accumulation of proliferating cell is not extensive and the donor cells do not that acquire effector functions. We previously showed that a single costimulatory signal delivered by an agonist Ab to OX40 (CD134) promotes accumulation of proliferating cells and promotes differentiation to effector CD4 T cells capable of secreting IFN-γ. In this study, we determined whether OX40 costimulation requires supporting costimulatory or differentiation signals to drive acquisition of effector T cell function. We report that OX40 engagement drives effector T cell differentiation in the absence of CD28 and CD40 signals. Two important regulators of Th1 differentiation, IL-12R and T-bet, also are not required for acquisition of effector function in CD4 T cells responsive to OX40 stimulation. Finally, we show that CD25-deficient CD4 T cells produce little IFN-γ in the presence of OX40 costimulation compared with wild type, suggesting that IL-2R signalling is required for efficient OX40-mediated differentiation to IFN-γ secretion.

Original languageEnglish (US)
Pages (from-to)7694-7702
Number of pages9
JournalJournal of Immunology
Volume178
Issue number12
StatePublished - Jun 15 2007

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Williams, C. A., Murray, S. E., Weinberg, A. D., & Parker, D. C. (2007). OX40-mediated differentiation to effector function requires IL-2 receptor signaling but not CD28, CD40, IL-12Rβ2, or T-bet. Journal of Immunology, 178(12), 7694-7702.