Expression of the T-cell activation antigen, OX-40, identifies alloreactive T cells in acute graft-versus-host disease.
The OX-40 molecule is expressed on the surface of recently activated T lymphocytes. The presence of OX-40 on CD4+ T cells was analyzed in a rat haplo-identical (parental --> F1) bone marrow transplant model of acute graft-versus-host disease (aGVHD). Increased numbers of activated CD4+ T cells that expressed the OX-40 antigen were detected in peripheral blood soon after transplantation before the earliest sign of disease. The peak of OX-40 expression occurred 12 days posttransplantation with a range of 18% to 36% of circulating T cells and remained 10-fold above background, never returning to baseline. A slight increase in OX-40 expression (range, 1% to 6%) was also detected on peripheral blood lymphocytes from control syngeneic F1 --> F1 recipients. OX-40+ T cells were isolated from spleen, skin, lymph node, and liver tissue of rats undergoing aGVHD, but not in syngeneic transplants. OX-40+ T cells isolated from these tissues were of donor origin and were shown to be alloreactive. These data raise the possibility of using the OX-40 antibody to detect and deplete selectively the T cells that cause aGVHD.
Tittle
T V
TV
Veterans Affairs Medical Center, Portland, OR, USA.
Weinberg
A D
AD
Steinkeler
C N
CN
Maziarz
R T
RT
D000818:Animals; D015415:Biomarkers; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002469:Cell Separation; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion / Q000379:methods; D011828:Radiation Chimera; D051381:Rats; D011915:Rats, Inbred BUF; D011917:Rats, Inbred Lew; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D015415:Biomarkers; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505718:Tnfrsf4 protein, rat; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7