ACTIVATION OF NON MHC-RESTRICTED CYTOTOXIC LYMPHOCYTES

确定细胞毒性和其他功能的机制 NK细胞的亚群或未成熟的前体细胞受 淋巴因子是了解这些细胞所起作用的先决条件。 在生理和病理条件下或在领养期间 免疫疗法与生物反应调节剂的结合。我们有 定义了一种体外培养系统，在该系统中成熟的NK细胞，和/或 外周血中NK和T细胞亚群比例较低 血液被诱导增殖，并将一种新的 细胞因子，操作上称为NKSF。NKSF是NK的有力调节者 细胞，它独立于IL-2影响其功能 (细胞毒性)，协同作用(诱导淋巴因子产生)或 对抗其影响(扩散)。为了定义分子 IL-2和NKSF对NK细胞作用机制的研究 功能，我们建议：a)识别淋巴因子和细胞毒分子 IL-2对其表达的差异性调控 NKSF，并分析了两者诱导的分子基础 淋巴因子，b)确定NKSF抑制的机制(S) IL-2诱导细胞增殖。NKSF不是NK细胞特异性的。要定义 白细胞亚群对NKSF敏感，我们将研究其对T细胞的影响 以及它们的一些子集(特别是那些可由IL-2诱导的子集 MHC-非限制性细胞毒性)，我们将尝试生产单克隆性 抗NKSF受体的抗体。我们观察到，在我们的文化体系中， NK表型的细胞被诱导从耗尽的PBL中增殖 成熟的NK细胞。我们的工作假设是NK细胞前体细胞是 诱导在这些条件下进行区分，我们将测试这一点 通过分析它们在外周血和骨骼中的存在情况提出假说 骨髓。从这里提出的研究中，我们希望能衍生出小说 关于NK细胞的生物学和不同的作用的信息 淋巴因子可增强这些细胞和其他细胞毒细胞的功能 类型。

Defining the mechanisms whereby cytotoxicity and other functions of NK cells, their subpopulations or immature precursors, are modulated by lymphokines is a prerequisite to understand the role played by these cells in physiological and pathological conditions or during adoptive immunotherapy in conjunction with biological response modifiers. We have defined an in vitro culture system in which mature NK cells, and/or subpopulations of NK and T cells present in low proportion in peripheral blood, are induced to proliferate and have purified to homogeneity a novel cytokine, operationally termed NKSF. NKSF is a potent regulator of NK cells, of which it affects functions independently from IL-2 (cytotoxicity), in synergy with it (induction of lymphokine production) or antagonizing its effects (proliferation). In order to define the molecular mechanisms that contribute to the effects of IL-2 and NKSF on NK cell functions, we propose: a) to identify lymphokines and cytotoxic molecules whose expression is differentially modulated by IL-2 in comparison with NKSF and analyze the molecular basis for their induction by the two lymphokines, b) to determine the mechanism(s) by which NKSF inhibits IL-2-induced proliferation. NKSF is not NK-cell specific. To define leucocyte subsets sensitive to NKSF, we will study its effect on T cells and some of their subsets (in particular those inducible by IL-2 to mediate MHC-non restricted cytotoxicity) and we will attempt to produce monoclonal antibodies to the NKSF-receptor. We observed that, in our culture system, cells with NK phenotype are induced to proliferate from PBL depleted of mature NK cells. It is our working hypothesis that NK cell precursors are induced to differentiate in these conditions, and we will test this hypothesis by analyzing their presence both in peripheral blood and bone marrow. From the studies proposed here, we expect to derive novel information on the biology of NK cells and on the role that distinct lymphokines play to enhance functions of these and other cytotoxic cell types.