OX40 controls functionally different T cell subsets and their resistance to depletion therapy

Alexander Kroemer, Xiang Xiao, Diem Vu Minh, Wenda Gao, Keisuke Minamimura, Ming Chen, Takashi Maki, Xian Chang Li

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

T cell depletion is a widely used approach in clinical transplantation. However, not all T cells are equally sensitive to depletion therapies and a significant fraction of T cells persists even after aggressive treatment. The functional attributes of such T cells and the mechanisms responsible for their resistance to depletion are poorly studied. In the present study, we showed that CD4+ T cells that are resistant to polyclonal anti-lymphocyte serum (ALS) mediated depletion exhibit phenotypic features of memory cells and uniformly express OX40 on the cell surface. Studies using the foxp3gfp knockin mice revealed that the remaining CD4+OX40+ cells consist of Foxp3+ Tregs and Foxp3- T effector/memory cells. The ALS-resistant CD4+OX40+ cells failed to mediate skin allograft rejection upon adoptive transferring into congenic Rag-/- mice, but removal of Foxp3+ Tregs from the OX40+ cells resulted in prompt skin allograft rejection. Importantly, OX40 is critical to survival of both Foxp3+ Tregs and T effector/memory cells. However, OX40 exhibits opposing effects on the functional status of Foxp3+ Tregs and T effector/memory cells, as stimulation of OX40 on T effector cells induced amplified cell proliferation but stimulation of OX40 on the Foxp3 + Tregs impaired their suppressor functions. Our study demonstrates that OX40 is a critical molecule in regulating survival and functions of depletionresistant T cells; and these findings may have important clinical implications.

Original languageEnglish (US)
Pages (from-to)5584-5591
Number of pages8
JournalJournal of Immunology
Volume179
Issue number8
DOIs
StatePublished - Oct 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'OX40 controls functionally different T cell subsets and their resistance to depletion therapy'. Together they form a unique fingerprint.

Cite this