In vitro evidence for disappearance of erythroid progenitor T suppressor cells following allogeneic bone marrow transplantation for severe aplastic anemia.
In vitro coculture studies were performed in five patients with severe aplastic anemia (SAA) and their normal HLA-matched donors before and after allogeneic bone marrow transplantation (BMT) to determine whether the erythropoietic function of T cells is abnormal in this disorder. These coculture studies used fresh or cryopreserved marrow T lymphocytes with fresh or cryopreserved marrow T cell-depleted target cells. Four of five aplastic patients had little or no transfusion exposure before studies. The composite results showed that, in comparison to the erythropoietic effects of normal HLA-identical marrow T lymphocytes or engrafted T lymphocytes, T lymphocytes collected from the aplastic patients before BMT consistently suppressed or failed to support CFUE and BFUE growth optimally from autologous marrow, HLA-identical marrow, or engrafted aplastic T cell-depleted marrows. This T cell abnormality was not observed in four multiply transfused leukemics and three patients with myelodysplastic syndrome. Marker analyses of SAA marrow T lymphocytes performed before and after BMT suggested that the erythropoietic functional abnormality was due to abnormal marrow T cell composition reflecting an excess of activated Tac+, T3+, T11+ lymphocytes. Collectively, these in vitro studies provide firmer in vitro evidence implicating T cells in the pathogenesis of SAA. The erythropoietic T cells abnormalities in SAA are fully corrected by allogeneic BMT.
D000741:Anemia, Aplastic / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000954:Antigens, Surface / Q000032:analysis; D001327:Autoimmune Diseases / Q000628:therapy*; D001853:Bone Marrow / Q000473:pathology; D016026:Bone Marrow Transplantation; D003114:Colony-Forming Units Assay; D004920:Erythropoiesis; D006801:Humans; D007938:Leukemia / Q000473:pathology; D009190:Myelodysplastic Syndromes / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*; D014019:Tissue Donors
D000954:Antigens, Surface