IMMATURE T LYMPHOCYTES IN THE PERIPHERAL BLOOD OF BONE MARROW TRANSPLANT RECIPIENTS1

Abstract
Recipients of allogeneic bone marrow transplants are characterized by an immunodeficiency of varying intensity and duration. The presence of in vivo activated suppressor T lymphocytes was demonstrated in immunodeficient patients with chronic graft-vs.-host disease. To determine the basis of the immunodeficiency of transplant recipients early after transplantation, the lymphocytes of transplant recipients were analyzed phenotypically by E[erythrocyte]-rosette formation and staiing with monoclonal antibodies (OKT-3, -6, and -8) and functionally by their blastogenic response to mitogens. Only 15% of transplant recipients'' assays 0-3 mo. and 16% of assays 3-12 mo. following transplant were in the normal range. Transplant recipients during the 1st yr after transplantation were characterized by an increased percentage (57%) of patients with a normal percentage of E-rosette-forming cells but reduced PHA [phytohemagglutinin] responsivness. In vitro coculture experiments demonstrated that their lack of PHA responsiveness was not due to the presence of in vivo activated suppressor cells or a decrease in mitogen-presenting cells. Staining with monoclonal antibodies revealed that the T lymphocytes from the majority of recipients at 0-3 mo. following transplantation contained a percentage of OKT8-positive cells greater than or equal to the percentage of OKT3-positive cells. This pattern (OKT8 .gtoreq. OKT3) was not found in the peripheral blood T lymphocytes of normal people but was found in 13 of 15 thymuses. Monoclonal staining with OKT6, a thymocyte-specific antibody, revealed positive staining of > 10% of the peripheral blood leukocytes in the majority of recipients 0-3 mo. following transplantation, compared with only a few normals. The circulating T lymphocytes of transplant recipients are phenotypically and functionally immature. Their relative immaturity contributes to the transplant recipients'' immunodeficiency.