OX40 (CD134) engagement drives differentiation of CD4+ T cells to effector cells

Cortny A. Huddleston, Andrew D. Weinberg, David Parker

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Naive, CD4+ T cells proliferate extensively but fail to differentiate when they are transferred into unirradiated recipients that express alloantigen or transgenic antigen on all MHC class II+ cells. Addition of an agonist antibody to OX40 (CD134), a costimulatory TNF receptor family member expressed on activated CD4+ T cells, enables the proliferating T cells to accumulate as differentiated effector cells and kill the host animals. The donor T cells from anti-OX40-treated animals express high levels of IL-2Rα (CD25) and acquire the ability to secrete IFN-γ when stimulated with IL-12 and IL-18. OX40 promotes differentiation by 48 h in T cell priming, before changes in Bcl-2 expression or cell recovery become apparent. We found that a Bcl-2 transgene or deficiency in Fas or TNFR1 failed to influence accumulation of differentiated donor cells, and found larger changes in expression of cytokine and cytokine receptor genes than in survival genes. Accumulation of differentiated CD4+ effector T cells is initiated directly through OX40, but some OX40-deficient donor cells can gain effector function as bystanders to OX40+/+ cells. Taken together, these data suggest that CD4+ T cell differentiation to effector function is an important effect of OX40 engagement under conditions of ubiquitous antigen presentation.

Original languageEnglish (US)
Pages (from-to)1093-1103
Number of pages11
JournalEuropean Journal of Immunology
Volume36
Issue number5
DOIs
Publication statusPublished - May 2006

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Keywords

  • Cell differentiation
  • Costimulation
  • Cytokine receptors
  • Graft versus host disease
  • Tolerance

ASJC Scopus subject areas

  • Immunology

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