ACTIVATION OF NON MHC-RESTRICTED CYTOTOXIC LYMPHOCYTES

非MHC限制性的体外模型系统的定义 细胞毒性细胞是在淋巴细胞增殖的条件下产生的。 刺激是理解 细胞毒性细胞的谱系和生物学， 调节它们的增殖和激活， 发生在体内不同细胞之间的病理情况 免疫系统和非免疫系统的类型效应器。 我们开发了一种体外系统， 产生细胞毒性细胞，这取决于内源性IL-2 从共培养的外周血单核细胞中产生 与B类淋巴母细胞系，即使这些缺乏I类HLA 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细胞的特征。 而且我们 观察到B类淋巴母细胞系组成性地产生一种 增强NK细胞几种功能特性的因子， 其中包括细胞毒活性、淋巴因子的产生 和扩散。 这个因素明显不同于其他已知的因素。 淋巴因子如IL-2、干扰素（IFN）或光毒素（LT）。 我们的假设是，在体内，增殖， NK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（其中可能有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细胞自身产生， 细胞相互作用或IL-2刺激。 我们开发的系统 我们观察到NKSF，一种与IL-2不同的因子， 激活NK细胞提供了一个机会，研究调节 NK细胞在类似条件下的活化和增殖 可能存在于病理性体内情况中的那些，其中 最小的抗原差异可诱导淋巴细胞活化。 这些研究旨在表征我们的体外模型和NKSF 应该提供关于NK细胞生物学的信息， 有效增加其数量的实际可能性， 功能协调发展的

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.