Meadows Sarah K, Eriksson Mikael, Barber Amorette, Sentman Charles L
Department of Microbiology and Immunology, Dartmouth Medical School, 6W Borwell Bldg, One Medical Center Drive, Lebanon, NH 03756, USA.
Int Immunopharmacol. 2006 Jun;6(6):1020-8. doi: 10.1016/j.intimp.2006.01.013. Epub 2006 Feb 17.
NK cells are an important component of innate immunity, and they can promote CTL and Th1 cell development and macrophage activation via cytokines. TGF-beta is believed to be an important immunoregulatory molecule, and for this reason several TGF-beta inhibitors are currently in clinical development. However, the modulation of specific innate immune responses by endogenous human TGF-beta remains unclear. In this study, we demonstrate that blocking the action of endogenous TGF-beta resulted in an increase in both the percentage of responding NK cells and the amount of IFN-gamma produced by human NK cells when stimulated by monokines and TLR agonists. Blocking endogenous TGF-beta resulted in significant NK cell IFN-gamma production under suboptimal stimulation conditions. Our findings also suggest that TGF-beta associated with other blood cells may be involved in limiting NK cell activation. Thus, inhibiting endogenous TGF-beta provides a means to shift NK cell activation and promote cellular immunity.
自然杀伤细胞（NK细胞）是先天性免疫的重要组成部分，它们可以通过细胞因子促进细胞毒性T淋巴细胞（CTL）和辅助性T细胞1（Th1）的发育以及巨噬细胞的激活。转化生长因子-β（TGF-β）被认为是一种重要的免疫调节分子，因此目前有几种TGF-β抑制剂正处于临床开发阶段。然而，内源性人TGF-β对特定先天性免疫反应的调节作用仍不清楚。在本研究中，我们证明，阻断内源性TGF-β的作用会导致在受到单核因子和Toll样受体（TLR）激动剂刺激时，应答性NK细胞的百分比以及人NK细胞产生的γ干扰素（IFN-γ）量均增加。在次优刺激条件下，阻断内源性TGF-β会导致显著的NK细胞IFN-γ产生。我们的研究结果还表明，与其他血细胞相关的TGF-β可能参与限制NK细胞的激活。因此，抑制内源性TGF-β提供了一种改变NK细胞激活并促进细胞免疫的方法。
