Role of Immunocompetent Cells in the Regulation of Human Megakaryocytopoiesis In Vitro
T cells and monocytes/macrophages (Mo) have been shown to play important roles in modulating the growth and differentiation of human erythroid and myeloid progenitors and have been implicated in the mechanisms of gamma interferon (γ-IFN) mediated suppression of normal human marrow erythroid progenitors in vitro. In order to assess the importance of T cells and Mo in the growth of human megakaryocytic progenitors (CFU-Mk) in vitro and to investigate γ-IFN effect on human megakaryocytopoiesis, normal human marrow (BM) was cultured in plasma clot in the presence and absence T cells, Mo and γ-IFN under conditions that support the formation of CFU-Mk derived colonies. The removal of T cells from BM (BM-T) caused a significant decrease (71.3 ±3.2 colonies observed vs 231.2 ± 38.5 colonies predicted) in both the number and size of CFU-Mk derived colonies, and no such changes were seen with Mo depletion (BM-Mo); co-culture of autologous T cells with BM depleted of both Mo and T cells (BM-Mo-T) caused a significant increase in CFU-Mk derived colonies and restored colony size. The addition of γ-IFN (<50–10,000 IU/ml) to BM caused a dose dependent inhibition of CFU-Mk (0–90%) as evidenced by decreased colony numbers and reduced colony size. The addition of γ-IFN (50–10,000 IU/ml) to BM-T caused reduced inhibition of CFU-Mk (0–60%); co-culture of T cells (but not Mo) pre-incubated with γ-IFN (10,000 IU/ml; 1 hour, 37 C followed by washing X 3) resulted in supression of CFU-Mk (80% inhibition with the addition of 1:4 T cells:marrow cells).
The results demonstrate that T cells have the ability to modulate the growth of human CFU-Mk in vitro and may, under appropriate conditions, either promote (normal T cells) or inhibit (γ-IFN activated T Cells) human megakaryocytopoiesis.
KeywordsColony Formation Colony Size Normal Human Bone Marrow Human Megakaryocyte Total Mononuclear Cell
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- 1.Lipton, J. and D. Nathan. 1985. Interaction between lymphocytes and macrophages in hematopoiesis. In Hematopoietic Stem Cells. D. Golde and F. Takaku, editors. Marcel Dekker, New York. 145–202.Google Scholar
- 5.Ascensao, J., N. Kay, M. Banisadre, and E. Zanjani. 1981. Cell-Cell interaction in human granulopoiesis: role of T lymphocytes. Exp. Hematology 9: 473–478.Google Scholar
- 11.Piacibello, W., L. Lu, B. Rubin, and H. Broxmeyer. 1984. Human gamma interferon enhances the release of granulocyte-macrophage colony stimulating factors (GM-CSF) from a sorted population of 0KT4+ lymphocytes stimulated by phytohemagglutinin (PHA). Blood 64 (Suppl): 455.Google Scholar
- 15.Broxmeyer, H., L. Lu, E. Platzer, C. Feit, L. Juliano, and R. Rubin. 1983. Comparative analysis of the influences of human gamma, alpha and beta interferons on human multipotential (CFU-GEMM), erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. J. Immunol. 131: 1300–1305.PubMedGoogle Scholar
- 16.Lu, L., K. Welte, J. Gabrilove, G. Hangoc, E. Bruno, R. Hoffman, and H. Broxmeyer. 1986. Effects of recombinant human tumor necrosis factor alpha, recombinant human gamma-interferon, and prostaglandin E on colony formation of human hematopoietic progenitor cells stimulated by natural human pluripotent colony — stimulating factor, pluripoietin alpha, and recombinant erythropoietin in serum-free cultures. Cancer Research 46: 4357–4361.PubMedGoogle Scholar
- 20.Kanz, L., G. Lohr, A. Fauser. 1983. Modulation of human megakaryocytic colony formation. In Normal and Neoplastic Hematopoiesis. D. Golde and P. Marks, editors. Alan R. Liss, Inc., New York 359–368.Google Scholar
- 21.Gewirtz, A., K. Mangan, and Y. Wen. 1986. Cellular regulation of in vitro human megakaryocytopoiesis. Clin. Res. 34: 458A.Google Scholar
- 22.Geissler, D., L.Lu, E. Bruno, H. Yank, H. Broxmeyer, and R. Hoffman. 1985. The influence of T-lymphocyte subsets and humoral factors on colony formation by human bone marrow and blood megakaryocyte progenitor cells in vitro. Blood 66. (Suppl): 452.Google Scholar