Enhancing effects of cyclosporin A on hematopoietic progenitors: possible role of CD8+ T cells as negative regulators.
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.
Hashimoto
F
F
First Department of Pathology, Kansai Medical University, Osaka, Japan.
Sugiura
K
K
Inoue
K
K
Ikehara
S
S
D000818:Animals; D001854:Bone Marrow Cells; D016827:CD8 Antigens / Q000032:analysis*; D016572:Cyclosporine / Q000494:pharmacology*; D015672:Erythroid Precursor Cells / Q000187:drug effects; D005260:Female; D006098:Granulocytes / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000276:immunology; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology*
D016827:CD8 Antigens; D016572:Cyclosporine