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 o f acute graft-versus-host disease (aGVHD), Increased numbers of activa ted CD4(+) T cells that expressed the OX-40 antigen were detected in p eripheral blood soon after transplantation before the earliest sign of disease. The peak of OX-40 expression occurred 12 days posttransplant ation with a range of 18% to 36% of circulating T cells and remained 1 0-fold above background, never returning to baseline, A slight increas e in OX-40 expression (range, 1% to 6%) was also detected on periphera l blood lymphocytes from control syngeneic Fl --> Fl recipients, OX-40 (+) T cells were isolated from spleen, skin, lymph node, end liver tis sue of rats undergoing aGVHD, but not in syngeneic transplants, OX-40( +) T cells isolated from these tissues were of donor origin and were s hown to be alloreactive, These data raise the possibility of using the OX-40 antibody to detect and deplete selectively the T cells that cau se aGVHD. (C) 1997 by The American Society of Hematology.