CD25 expression distinguishes functionally distinct alloreactive CD4+ CD134+ (OX40+) T-cell subsets in acute graft-versus-host disease

Philip R. Streeter, Xingqi Zhang, Thomas V. Tittle, Catherine N. Schön, Andrew D. Weinberg, Richard T. Maziarz

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

CD134 (OX40) is expressed on activated CD4+ donor T cells in allogeneic stem cell transplant recipients with acute graft-versus-host disease. The data presented here reveal that differential expression of CD25 by CD4+ CD134+ T cells allows separation of these activated cells into 2 phenotypically and functionally distinct alloreactive T-cell subsets. These subsets exhibit distinct tissue associations, with CD4+ CD134+ CD25- T cells preferentially found in lymphoid tissues and CD4+ CD134+ CD25+ T cells located in lymphoid tissues and inflamed extralymphoid tissues. The CD25- T-cell subset exhibited potent proliferative responses to both concanavalin A and allogeneic host leukocytes. By contrast, the CD25+ T-cell subset proliferated minimally in response to either treatment and inhibited alloantigen-induced proliferation of the CD25- subset. Proliferative unresponsiveness associated with the CD25+ T-cell subset did not extend to cytokine secretion. When stimulated with alloantigen, both CD4+ CD134+ T-cell subsets responded by secreting interferon-γ and interleukin (IL)-10, and neither T-cell subset produced detectable levels of IL-2 or IL-4. Three-day treatment of the CD25+ T-cell subset with IL-2 restored the proliferative responsiveness of these cells to host alloantigens, suggesting that the proliferative unresponsiveness associated with this T-cell subset reflected a requirement for IL-2. The preferential tissue associations and distinct functional properties associated with these separable alloreactive CD4+ CD134+ T-cell subsets suggest that they participate differentially in clinical graft-versus-host disease.

Original languageEnglish (US)
Pages (from-to)298-309
Number of pages12
JournalBiology of Blood and Marrow Transplantation
Volume10
Issue number5
DOIs
StatePublished - May 1 2004

Keywords

  • Allogeneic stem cell transplantation
  • CD134
  • Graft-versus-host disease
  • OX40

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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