In vitro evidence for disappearance of erythroid progenitor T suppressor cells following allogeneic bone marrow transplantation for severe aplastic anemia

Abstract

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.

Observation of serum estradiol testosterone and immune function in aplastic anemia

“…"Extra-sexual actions" of E2 in ITP, SLE have been confirmed [1,21. As for AA, there 0 1993 Wiley-Liss, Inc. [4], and estrogen could promote the immune response and induce autoimmune disorders in humans [5-71, our finding probably resulted from immune reaction. Cohen et al [8] have described the estrogen receptor in the thymus and lymphocyte, especially in the T cell.…”

“…American reports [ 1-31 but has never been reported in Chinese patients, although Chinese researchers provided the first and the largest series report [4,5]. The hyperleukocytosis may lead to clinical signs of leukostasis and fatal outcome if the leukocyte count is not rapidly reduced.…”

Human hemopoietic growth factors

“…In hematologic disease, CSF are detected in urine from human patients or dogs with cyclic neutropenia (55, 56), patients with severe aplastic anemia (SAA) (57) and during the first days after bone marrow transplantation (58). In SAA, autoimmune mechanisms rather than a defect in humoral factors like CSF are probably the pathogenetic principle (59)(60)(61).…”

“…Aplastic anemia or cyclic hematopoiesis are unlikely to be related to a defect in growth factor production, because CSF are often detected in serum or urine from these patients. Yet, in aplastic anemia, soluble factors and cellular interactions have been implicated in inhibition of hematopoiesis (59,60,108). In this regard, the inhibitory action of moderate concentrations of several cytokines on hematopoietic progenitors can at least partially be overcome by high concentrations of growth factors, suggesting that CSF application could be effective in at least a subset of SAA patients.…”

Mechanism of action of antithymocyte globulin in the treatment of aplastic anaemia: in vitro evidence for the presence of immunosuppressive mechanism

“…(2) an immunostimulatory effect of ATG on T lymphocytes, resulting in release of haemopoietic growth factors such as interleukin-3 (IL-3) and granulocyte/macrophage colonystimulating factor (GM-CSF) (Abe et al, 1991;Nimer et al, 1991); (3) the release of IL-1 and IL-6 from monocytes by ATG (Rameshwar et al, 1992); and (4) a direct stimulatory effect of ATG on the growth of haemopoietic stem and progenitor cells (Huang et al, 1987(Huang et al, , 1994. Among them, the immunosuppressive effect appears to be the major mechanism of ATG treatment, since there is much clinical and laboratory evidence of the existence of T lymphocytes which suppress haemopoiesis in AA (Thomas et al, 1976;Speck et al, 1976;Hoffman et al, 1977;Lu et al, 1981;Zoumbos et al, 1985a;Mangan et al, 1988). The aim of the present study was to determine whether such an immunosuppressive mechanism is present in patients with AA who are successfully treated with ATG.…”