Triggering of OX40 (CD134) on CD4+CD25+ T cells blocks their inhibitory activity: A novel regulatory role for OX40 and its comparison with GITR

Barbara Valzasina, Cristiana Guiducci, Heidrun Dislich, Nigel Killeen, Andrew D. Weinberg, Mario P. Colombo

Research output: Contribution to journalArticlepeer-review

Abstract

OX40 (CD134) is a member of the tumor necrosis factor (TNF) receptor family that is transiently expressed on T cells after T-cell receptor (TCR) ligation. Both naive and activated CD4+CD25+ regulatory T cells (T reg's) express OX40 but its functional role has not been determined. Since glucocorticoid-induced tumor necrosis factor receptor (GITR), a related TNF receptor family member, influences T reg function, we tested whether OX40 might have similar effect. Triggering either GITR or OX40 on T reg's using agonist antibodies inhibited their capacity to suppress and restored effector T-cell proliferation, interleukin-2 (IL-2) gene transcription and cytokine production. OX40 abrogation of T reg suppression was confirmed in vivo in a model of graft-versus-host disease (GVHD). In a fully allogeneic C57BL/6>BALB/c bone marrow transplantation, GVHD was lethal unless T reg's were cotransferred with the bone marrow and effector T cells. Strikingly, T reg suppression of GVHD was abrogated either by intraperitoneal injection of anti-OX40 or anti-GITR monoclonal antibodies (mAbs) immediately after transfer, or by in vitro pretreatment of T reg's with the same mAbs before transfer. Cumulatively, the results suggest that in addition to controlling memory T-cell numbers, OX40 directly controls T reg-mediated suppression.

Original languageEnglish
Pages (from-to)2845-2851
Number of pages7
JournalBlood
Volume105
Issue number7
DOIs
Publication statusPublished - Apr 1 2005

ASJC Scopus subject areas

  • Hematology

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