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. We have previously demonstrated the presence of in vivo activated suppressor T lymphocytes in immunodeficient patients with chronic graft-versushost disease. To determine the basis of the immunodeficiency of transplant recipients early after transplantation, the lymphocytes of transplant recipients were analyzed phenotypically by E-rosette formation and staining with monoclonal antibodies (OKT-3, -6, and -8) and functionally by their blastogenic response to mitogens. Only 15% of transplant recipients' assays 0-3 months and 16% of assays 3-12 months following transplant were in the normal range. Transplant recipients during the first year after transplantation were characterized by an increased percentage (57%) of patients with a normal percentage of E-rosette-forming cells but reduced PHA responsiveness. 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 months following transplantation contained a percentage of OKT8-positive cells greater than or equal to the percentage of OKT3-positive cells. This pattern (OKT8 ≥ 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 more than 10% of the peripheral blood leukocytes in the majority of recipients 0-3 months following transplantation, compared with only a few normals. We concluded that the circulating T lymphocytes of transplant recipients are phenotypically and functionally immature, and that their relative immaturity contributes to the transplant recipients' immunodeficiency.