title: CD25 expression distinguishes functionally distinct alloreactive CD4 CD134 (OX40) T-cell subsets in acute graft-versus-host disease.
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-gamma 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.
authors.affiliation: Department of Medicine, Oregon Health and Science University, Portland, OR 97239, USA. streetep@ohsu.edu
authors.forename: Philip R
authors.initials: PR
authors.lastname: Streeter
authors.forename: Xingqi
authors.initials: X
authors.lastname: Zhang
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Tittle
authors.forename: Catherine N
authors.initials: CN
authors.lastname: Schön
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Weinberg
authors.forename: Richard T
authors.initials: RT
authors.lastname: Maziarz
mesh_terms: D000208:Acute Disease; D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D007109:Immunity; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion / Q000009:adverse effects; D051381:Rats; D011919:Rats, Inbred Strains; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014018:Tissue Distribution
chemical_list: D016207:Cytokines; D015375:Receptors, Interleukin-2; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C505718:Tnfrsf4 protein, rat