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

1996; Mary Ann Liebert, Inc.; Volume: 12; Issue: 7 Linguagem: Inglês

10.1089/aid.1996.12.577

1931-8405

R. G. Geißler, Rita Rossol, Ulrich Mentzel, Oliver G. Ottmann, Andreas Klein, Peter Gute, E. B. Helm, D. Hoelzer, Arnold Ganser,

Immunodeficiency and Autoimmune Disorders

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.