Role of immunocompetent cells in the regulation of human megakaryocytopoiesis in vitro.

Abstract

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 (gamma-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 gamma-IFN effect on human megakaryocytopoiesis, normal human marrow (BM) was cultured in plasma clot in the presence and absence T cells, Mo and gamma-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 gamma-IFN (less than 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 gamma-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 gamma-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 (gamma-IFN activated T Cells) human megakaryocytopoiesis.