Hansz J, Kozlowska-Skrzypczak M
Department of Hematology, Academy of Medicine, Poznań, Poland.
Immunobiology. 1992 Nov;186(3-4):327-38. doi: 10.1016/S0171-2985(11)80261-5.
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.
在本研究中，我们采用血浆凝块扩散小室（DC）技术，在体内培养中检测了急性髓系白血病（AML）患者外周血T淋巴细胞对骨髓来源的红系祖细胞（BFU-DE和CFU-DE）生长的影响。双室小室（每个室由膜滤器分隔）的应用使得研究T淋巴细胞对骨髓红系祖细胞增殖的体液效应成为可能。在缺乏统计学上显著数量单核细胞的情况下，AML患者的T淋巴细胞抑制了来自T淋巴细胞和贴壁细胞耗竭骨髓的BFU-DE和CFU-DE的生长。抑制能力仅限于通过阴性选择技术从T细胞获得的CD4阳性富集组分。相反，CD8阳性富集组分对红系集落形成没有影响。自体和异体的BFU-DE和CFU-DE受到CD4阳性T细胞的类似影响。在共培养前用抗HLA-DR单克隆抗体处理T细胞，完全消除了对BFU-DE和CFU-DE衍生集落形成的抑制。用抗干扰素-γ抗体处理也完全消除了在CD4阳性T细胞中检测到的抑制活性；而在30 Gy辐射后抑制作用仍然存在。在这些实验条件下，健康受试者的静息T淋巴细胞不影响红系集落形成。我们的数据表明，在AML患者中，CD4阳性T细胞内循环的HLA-DR阳性、辐射敏感性较低的亚群能够诱导干扰素-γ介导的红细胞生成抑制，至少在DC培养中是这样。
