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  • Title: Enhancing effects of cyclosporin A on hematopoietic progenitors: possible role of CD8+ T cells as negative regulators.
    Author: Hashimoto F, Sugiura K, Inoue K, Ikehara S.
    Journal: Exp Hematol; 1994 Sep; 22(10):947-53. PubMed ID: 8088377.
    Abstract:
    To elucidate the mechanism by which the administration of cyclosporin A (Cy A) improves a certain type of anemia, Cy A was orally administered to normal mice; hematopoietic activity, natural killer (NK) cell activity, and natural suppressor (NS) cell activity in the bone marrow (BM) were then examined. Hematopoietic colony formation was significantly enhanced by both 7-day and 21-day treatment with Cy A. Cy A did not, however, affect the total cell count or the numbers of macrophages, granulocytes, or B cells in the BM. Neither did Cy A affect the in vitro colony formation of the purified hematopoietic progenitors. These results suggest that Cy A acts on the negative regulators such as NK cells, NS cells, and CD8+ T cells. Since both NK and NS activity were also enhanced by Cy A treatment, these cells were not candidates. CD4+ or CD8+ T cells in the thymus, peripheral blood (PBL), and BM decreased as a result of the treatment. Therefore, to further examine the involvement of CD4+ or CD8+ T cells, hematopoietic colony formation was evaluated using bone marrow cells (BMCs) from mice purged of CD4+ and/or CD8+ cells. A significant enhancement of erythroid and multipotent colonies was observed in the BM of the CD8+ cell-purged mice. On the other hand, a significant enhancement of myeloid colonies was found in the BM of the CD4+ cell-purged mice. These findings suggest that single-positive T cells (particularly CD8+ T cells), which are diminished in number after Cy A treatment, are involved in the negative regulation of hematopoiesis.
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