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The role of transforming growth factor beta in the generation of suppression: an interaction between CD8+ T and NK cells

机译:转化生长因子β在抑制产生中的作用:CD8 + T与NK细胞之间的相互作用

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摘要

CD8+ T cells have suppressor effector functions, but the mechanisms involved in the generation of this activity are poorly understood. We report that natural killer (NK) cells have an important role in the acquisition of this function. CD8+ cells induce NK cells to produce transforming growth factor-beta (TGF-beta) which, in turn, stimulates CD8+ T cells to become suppressors of antibody production. Using a monocyte-dependent and -independent method to induce antibody production, we first observed that the addition of NK cells to CD8+ cells was required for optimal suppression. Next, we determined that the interaction of CD8+ T cells with NK cells resulted in a striking increase NK cell TGF-beta mRNA and its production. This cytokine appeared to be involved in the induction of T suppressor cell activity since: (a) anti-TGF-beta 1 completely abrogated the suppression of immunoglobulin G synthesis; (b) TGF-beta 1 could substitute for NK cells in inducing CD8+ T cells to develop suppressor activity; and (c) a short exposure of T cells to TGF-beta 1 in the absence of B cells was sufficient for the generation of suppressor activity by CD8+ T cells. Interferon gamma did not have this property. These studies provide strong evidence that in addition to its suppressive properties, TGF- beta is involved in the generation of CD8+ T suppressor effector cells. Because NK cell function is decreased in many autoimmune diseases, these cells may fail to interact properly with these individuals' CD8+ cells in generating suppressors of aggressive anti-self responses.
机译:CD8 + T细胞具有抑制器效应功能,但对该活性的产生所涉及的机制了解甚少。我们报告自然杀手(NK)细胞在此功能的获取中具有重要作用。 CD8 +细胞诱导NK细胞产生转化生长因子-β(TGF-beta),进而刺激CD8 + T细胞成为抗体产生的抑制剂。我们首先使用单核细胞依赖性和非依赖性方法来诱导抗体产生,我们首先观察到需要将NK细胞添加到CD8 +细胞中才能获得最佳抑制效果。接下来,我们确定CD8 + T细胞与NK细胞的相互作用导致NK细胞TGF-βmRNA及其产生的惊人增加。该细胞因子似乎与T抑制细胞活性的诱导有关,因为:(a)抗TGF-β1完全废除了对免疫球蛋白G合成的抑制; (b)TGF-beta 1可以替代NK细胞,诱导CD8 + T细胞发挥抑制活性; (c)在不存在B细胞的情况下,T细胞短时间暴露于TGF-beta 1足以使CD8 + T细胞产生抑制活性。干扰素伽玛不具有此性质。这些研究提供了有力的证据,证明除了其抑制特性外,TGF-β还参与了CD8 + T抑制效应细胞的产生。由于在许多自身免疫性疾病中NK细胞功能下降,因此这些细胞可能无法与这些人的CD8 +细胞正确相互作用,从而无法产生积极的抗自身反应的抑制剂。

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