γδ-T Cell-Receptor-Positive Lymphocytes Inhibit Human Hematopoietic Progenitor Cell Growth in HIV Type 1-Infected Patients

Abstract

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 δTCS-1- and mostly CD-8-positive subpopulation of cytotoxic T-lymphocytes expressing the γδ-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 γδ-positive cells in HIV-associated bone marrow deficiency. The number of bone marrow-derived pluripotent colony-forming units (CFU-GEMM), burst-forming 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, γδ-positive, and δTCS-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-γ and tumor necrosis factor-α as the mechanisms mediating the suppressive effect of the δTCS-1-positive cells in HIV-positive patients.