In severe HIV infection, the majority of patients exhibit signs of hematopoietic deficiency including anemia, leukopenia, and thrombocytopenia. Besides other pathophysiological mechanisms, the disturbed helper/suppressor ratio of T-lymphocytes suggests that alterations within T cell subpopulations may have a suppressive effect on HIV-associated hematopoiesis. Since a delta TCS-1- and mostly CD-8-positive subpopulation of cytotoxic T-lymphocytes expressing the gamma delta-receptor is increased in peripheral blood and bone marrow of HIV-infected persons, it was the aim of this study to investigate the role of gamma delta-positive cells in HIV-associated bone marrow deficiency. The number of bone marrow-derived pluripotent colony-forming units (CFU-GEMM), burstforming units-erythrocyte (BFU-E), and colony-forming units-granulocyte-monocyte (CFU-GM) of HIV-1-positive patients was significantly (p < 0.05) increased after depletion of CD-8-positive, gamma delta-positive, and delta TCS-1-positive T-lymphocytes. In contrast, the depletion of these subpopulations had no stimulatory effect in healthy controls. Further experiments identified direct cellular contact between effector and hematopoietic progenitor cells and the production of interferon-gamma and tumor necrosis factor-alpha as the mechanisms mediating the suppressive effect of the delta TCS-1-positive cells in HIV-positive patients.
Adult Base Sequence