GAMMA-DELTA-T-CELL-RECEPTOR-POSITIVE LYMPHOCYTES INHIBIT HUMAN HEMATOPOIETIC PROGENITOR-CELL GROWTH IN HIV TYPE 1-INFECTED PATIENTS

In severe HIV infection, the majority of patients exhibit signs of hem atopoietic deficiency including anemia, leukopenia, and thrombocytopen ia. Besides other pathophysiological mechanisms, the disturbed helper/ suppressor ratio of T-lymphocytes suggests that alterations within T c ell subpopulations may have a suppressive effect on HIV-associated hem atopoiesis, Since a delta TCS-1- and mostly CD-8-positive subpopulatio n of cytotoxic T-lymphocytes expressing the gamma delta-receptor is in creased in peripheral blood and bone marrow of HIV-infected persons, i t was the aim of this study to investigate the role of gamma delta-pos itive cells in HIV-associated bone marrow deficiency, The number of bo ne marrow-derived pluripotent colony-forming units (CFU-GEMM), burst-f orming 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. F urther experiments identified direct cellular contact between effector and hematopoietic progenitor cells and the production of interferon-g amma and tumor necrosis factor-alpha as the mechanisms mediating the s uppressive effect of the delta TCS-1-positive cells in HIV-positive pa tients.