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 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.
Geissler
R G
RG
Department of Hematology, Medizinische Hochschule Hannover, Germany.
Rossol
R
R
Mentzel
U
U
Ottmann
O G
OG
Klein
A S
AS
Gute
P
P
Helm
E B
EB
Hoelzer
D
D
Ganser
A
A
D000328:Adult; D001483:Base Sequence; D001854:Bone Marrow Cells; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division; D002478:Cells, Cultured; D004279:DNA, Viral; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012194:RNA-Directed DNA Polymerase; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D004279:DNA, Viral; D016898:Interferon-alpha; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D012194:RNA-Directed DNA Polymerase