ACTIVATION OF NON MHC-RESTRICTED CYTOTOXIC LYMPHOCYTES

非MHC限制性体外模型体系的定义 细胞毒细胞是在淋巴细胞的条件下产生的 刺激是理解 细胞毒细胞的谱系和生物学 调节它们的增殖和激活，以及相互作用 在体内发生在不同细胞之间的病理情况 免疫系统和非免疫系统的效应器类型。 我们开发了一个体外系统，在这个系统中，大量的 细胞毒细胞的产生取决于内源性IL-2 外周血单核细胞共培养产生 B淋巴母细胞系，即使它们缺乏I类人类白细胞抗原 抗原。大多数，但不是全部，这些扩大的细胞毒性 淋巴细胞具有NK细胞的特性。此外，我们 观察到B淋巴母细胞系结构性地产生一种 增强NK细胞几种功能特性的因子， 其中有细胞毒活性，产生淋巴因子 和扩散。这一因素与其他已知因素明显不同。 淋巴因子，如IL-2、干扰素(IFN)或淋巴毒素(LT)。 我们的工作假设是，在活体内， 自然杀伤细胞和其他非正常细胞的分化和功能 定义的细胞毒性细胞类型(其中可能包括LAK细胞)是 不仅受IL-2的调节，还可能受其他细胞因子的调节 由辅助细胞或NK细胞本身产生，在 细胞相互作用或IL-2刺激。我们开发的系统 而我们观察到，NKSF，一个不同于IL-2的因素， 激活NK细胞提供了研究其调节的机会 NK细胞在相似条件下的活化和增殖 可能存在于体内病理情况下的那些 最小的抗原差异可能会诱导淋巴细胞活化。 这些研究提出了我们的体外模型和NKSF的特征 应提供有关NK细胞的生物学和 有效地增加它们的数量和 功能。

Definition of in vitro model systems in which non MHC-restricted cytotoxic cells are generated under conditions of lymphocytes' stimulation constitutes an essential tool for the understanding of the lineage and biology of the cytotoxic cells, of the factors regulating their proliferation and activation, and of the interplay occurring in vivo in pathological situations among different cell types effector of the immune and non immune system. We developed an in vitro system in which high numbers of cytotoxic cells are generated, depending on endogenous IL-2 production, from peripheral blood mononuclear cells cocultured with B lymphoblastoid lines, even if these lack class I HLA antigens. Most, but not all, of these expanded cytotoxic lymphocytes have characteristics of NK cells. Moreover, we observed that B lymphoblastoid lines constitutively produce a factor that potentiates several functional properties of NK cells, among which are cytotoxic activity, production of lymphokines and proliferation. This factor is clearly distinct from other known lymphokines such as IL-2, interferon (IFN) or lymphotoxin (LT). It is our working hypothesis that, in vivo, proliferation, differentiation and functions of NK cells and of other non well defined cytotoxic cell types (among which possibly LAK cells) are regulated not only by IL-2, but also by other cytokines, possibly produced by accessory cells or by the NK cells themselves, upon cellular interaction or IL-2 stimulation. The system we developed and our observation that NKSF, a factor distinct from IL-2, activates NK cells offer the opportunity to study the regulation of NK cell activation and proliferation under conditions similar to those possibly present in pathological in vivo situations in which minimal antigenic differences may induce lymphocyte activation. The studies proposed to characterize our in vitro model and NKSF should provide information on NK cells' biology and on the practical possibility of enhancing efficiently their number and functions.