Expression of CD134 (0X-40) on T cells during the first 100 days following allogeneic bone marrow transplantation as a marker for lymphocyte activation and therapy-resistant graft-versus-host disease.

CD134 (OX-40) is an activation-associated antigen which functions as a costimulatory receptor for CD4+ T cells. In order to determine the expression of CD134 during immune recovery following allogeneic bone marrow transplantation (BMT), we measured its expression on T cells and T cell subsets during the first 100 days following BMT in 26 patients. CD4+CD134+ T could be seen approximately 14 days following BMT cells in patients who did not develop GvHD which required therapy (n = 20). The percentage of CD4+CD134+ cells continued to increase up to the fourth week following BMT to a maximum of 40-50% of CD4+ T cells (normal = 1-8%). Two patients who developed Grade I-II GvHD and who responded to treatment with pulsed high-dose methylprednisolone (MPD) showed a decline of approximately 40% in CD4+CD134+ T cells was seen within 48 hours of treatment. Four patients who developed GvHD that was not responsive to MPD and who later developed high IV GvHD showed increasing CD4+CD134+ T cells up to 85% of the CD4+ T cells. Additionally, rapid increases in CD134+ T cells following antibody-based T cell therapy were associated with GvHD recurrence. In no cases was the percentage of CD134+ CD4+ T cells predictive of clinical GvHD. In this exploratory study, we have shown that CD134, although not predictive of the initial onset of GvHD, may be a useful tool for monitoring the response to early GvHD therapy and identification of patients at risk for reemergence of GvHD who may benefit from anti-T cell therapy. Cytometry (Comm. Clin. Cytometry) 38: 238-243, 1999.

Phenotypic and functional reconstitution of peripheral blood lymphocytes following T cell-depleted bone marrow transplantation from partially mismatched related donors.

Myeloablative chemotherapy followed by transplantation of a T cell-depleted bone marrow graft from a partially mismatched related donor provides a potentially curative option for patients with leukemia and other disorders of hematopoiesis, although the patient is faced with a period of sustained immunodeficiency as well as pharmacologic immunosuppression as a result of prophylaxis against graft-versus-host disease. Thirty patients who received one to three antigen T cell-depleted mismatched grafts were evaluated for immune reconstitution. The percentage and numbers of cells expressing lymphocyte subset antigens were determined by flow cytometry at 14, 28, 60, 100, 180, 270 and 365 days post-BMT and at 6 month intervals thereafter. Lymphocyte reconstitution was characterized by the early appearance of natural killer cells and a low percentage of both T and B cells. During the first year after BMT, the number of NK cells remained constant while T and B cells gradually returned to normal numbers and proportions. Response to the lymphocyte mitogen phytohemagglutinin returned to normal over the course of 2 years, while the response to concanavalin A was slightly depressed and the response to pokeweed mitogen became supranormal at about 1.5 years and continued to increase. These data suggest the need for long-term immunophenotypic monitoring as well as prolonged infection surveillance and prophylaxis.