Interferon-gamma-mediated suppression of erythroid progenitor growth by a HLA-DR- and CD4-positive subset of T lymphocytes in acute myeloid leukemia.
In this study, we examined the effects of peripheral blood T lymphocytes from patients with acute myeloid leukemia (AML) on marrow-derived erythroid progenitors (BFU-DE and CFU-DE) growth in an in vivo culture by using the plasma clot diffusion chamber (DC) technique. The application of double-compartment chambers (each compartment separated by a membrane filter) makes the investigations of humoral effects of T lymphocytes upon marrow erythroid progenitors proliferation possible. T lymphocytes of AML-patients in the absence of a statistically significant number of monocytes suppressed the growth of BFU-DE and CFU-DE from T lymphocyte- and adherent cell-depleted marrows. The inhibition ability was restricted to the CD4-positive enriched fraction obtained from T cells by using the negative selection technique. In contrast, the CD8-positive enriched fraction had no effect on erythroid colony formation. Autologous and allogeneic BFU-DE and CFU-DE were similarly affected by the CD4-positive T cells. Treatment of T cells with monoclonal antibodies against HLA-DR before cocultures, completely abrogated the suppression of BFU-DE and CFU-DE-derived colony formation. Suppressive activity detected in the CD4-positive T cells was also totally abolished by treatment with anti-interferon-gamma antibodies; whereas the inhibition was retained after 30 Gy radiation. Under these experimental conditions, resting T lymphocytes from healthy subjects did not affect the erythroid colony formation. Our data show that in AML-patients, a circulating HLA-DR-positive, less radiosensitive subset within the CD4-positive T cells is capable of inducing an interferon-gamma-mediated suppression of erythropoiesis, at least in DC culture.
Department of Hematology, Academy of Medicine, Poznań, Poland.
J
J
Hansz
M
M
Kozlowska-Skrzypczak
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004920:Erythropoiesis / Q000276:immunology*; D006684:HLA-DR Antigens / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000473:pathology*
D006684:HLA-DR Antigens; D007371:Interferon-gamma