Delfino D V, Lepri E, Ayroldi E, Migliorati G, Boggs S S, Riccardi C
Department of Clinical Medicine, Pathology, and Pharmacology, University of Perugia, Italy.
Exp Hematol. 1998 Jan;26(1):2-9.
The goal of the present work was to study the regulatory role of T lymphocytes on natural killer (NK) cell generation in NK long-term bone marrow cultures (LTBMCs), an established mouse long-term bone marrow (BM) culture system used for the study of NK cell differentiation from precursors. Activation of the few T cells present in NK-LTBMCs by addition of anti-CD3 monoclonal antibody (mAb) together with interleukin (IL)-2 inhibited the generation of NK cells. Coculture with NK-LTBMCs of a pure population of preactivated BM T cells completely inhibited NK cell development even when the T cells were separated from the NK-LTBMCs by transwells. Depletion of IL-2 by activated T cells was not the mechanism of the negative regulation because anti-CD3 mAb added to the cultures inhibited the generation of NK cells even in the presence of 10-fold higher concentrations of exogenous IL-2 than that used in controls. Medium from cultures in which suppression had occurred was also suppressive, suggesting that one or more soluble factors released in the medium was responsible. That this effect was exerted on NK cell development from precursors was indicated by the finding that T cell-conditioned medium stimulated proliferation of mature NK cells. In our experimental conditions, monoclonal antibodies to IL-10, IL-13, transforming growth factor-beta, and tumor necrosis factor receptor failed to reverse the inhibitory effect.
本研究的目的是探讨T淋巴细胞在自然杀伤（NK）细胞长期骨髓培养（LTBMC）中对NK细胞生成的调节作用，NK-LTBMC是一种已建立的小鼠长期骨髓（BM）培养系统，用于研究NK细胞从前体细胞的分化。通过添加抗CD3单克隆抗体（mAb）和白细胞介素（IL）-2激活NK-LTBMC中存在的少量T细胞，可抑制NK细胞的生成。将预激活的BM T细胞纯群体与NK-LTBMC共培养，即使T细胞通过transwell与NK-LTBMC分离，也能完全抑制NK细胞的发育。活化的T细胞消耗IL-2不是负调节的机制，因为即使在存在比对照中使用的外源性IL-2浓度高10倍的情况下，添加到培养物中的抗CD3 mAb也能抑制NK细胞的生成。发生抑制作用的培养物的培养基也具有抑制作用，这表明培养基中释放的一种或多种可溶性因子起了作用。T细胞条件培养基刺激成熟NK细胞增殖的发现表明，这种作用是对前体细胞的NK细胞发育产生的。在我们的实验条件下，针对IL-10、IL-13、转化生长因子-β和肿瘤坏死因子受体的单克隆抗体未能逆转抑制作用。
