Decreased hematopoietic accessory cell function following bone marrow transplantation

Hematologic engraftment following bone marrow transplantation requires not only pluripotent stem cells but also functioning accessory cells whose trophic factors support the proliferation and differentiation of stem cells and progenitors to mature blood cells. To better understand the regulation of hematopoiesis following transplantation, we studied hemopoietic accessory cell function in bone marrow transplant recipients 3 weeks to 10 months following transplantation. In general, hematopoietic accessory cell function was decreased following bone marrow transplantation. Sequential fractionation of accessory cells demonstrated that adherent cells often produced near-normal functional burst-promoting activity (BPA) and granulocyte-macrophage colony-stimulating activity (GM-CSA), but Fc receptor-positive (Fc+) cells and T cells uniformly produced greatly reduced BPA and GM-CSA, as compared to transplant donor cells. This cellular deficiency was corrected by soluble burst-promoting activity and granulocyte-macrophage colony-stimulating activity and so appeared to be due to the failure of accessory cells to produce trophic hormones. Limiting-dilution analysis (LDA) for proliferating T-cell precursors demonstrated a greatly reduced frequency in phytohemagglutinin-responsive cells, supporting the role of deficient hematopoietic growth factor production by activated T cells in transplant recipients. This hemopoietic accessory cell defect may thus reflect more generalized lymphocyte dysfunction in these patients. Hematopoiesis following bone marrow transplantation appears to rely upon growth factors released by accessory cells in the adherent layer.