Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany.
Eur J Immunol. 2014 Nov;44(11):3368-79. doi: 10.1002/eji.201444515. Epub 2014 Sep 19.
Monocytes are known to engage in reciprocal crosstalk with NK cells but their influence on NK-cell-associated antibody-dependent cellular cytotoxicity (ADCC) is not well understood. We demonstrate that in humans FcγRIII (CD16)-dependent ADCC by NK cells is considerably enhanced by monocytes, and that this effect is regulated by FcγRII (CD32) crosslinking in healthy individuals. It is known that during HIV-1 infection, NK cells are known to express low levels of CD16 and exhibit reduced ADCC. We show that immune regulation of CD16-mediated NK-cell cytotoxicity by monocytes through CD32 engagement is substantially disturbed in chronic progressive HIV-1 infection. Expression of activating isoform of CD32 represented a compensatory mechanism for reduced expression of CD16 on NK cells during HIV-1 infection. As a result, the regulation of NK-cell-associated ADCC by monocytes is skewed and eventually constitutes a novel factor that contributes to HIV-1-associated immune deficiency, dysregulation and pathogenesis. Our data therefore provide evidence, for the first time, that in humans monocytes act as a rheostat for FcγRIII-mediated NK-cell functions maintaining a well-balanced immune response.
单核细胞被认为与 NK 细胞之间存在相互交流，但它们对 NK 细胞相关抗体依赖的细胞毒性（ADCC）的影响尚未得到很好的理解。我们证明，在人类中，NK 细胞通过 FcγRIII（CD16）依赖性 ADCC 显著增强，而这种效应在健康个体中受到 FcγRII（CD32）交联的调节。众所周知，在 HIV-1 感染期间，NK 细胞表达低水平的 CD16 并表现出降低的 ADCC。我们表明，单核细胞通过 CD32 交联对 CD16 介导的 NK 细胞细胞毒性的免疫调节在慢性进行性 HIV-1 感染中受到严重干扰。CD32 表达的激活同工型代表了 HIV-1 感染期间 NK 细胞上 CD16 表达降低的补偿机制。结果，单核细胞对 NK 细胞相关 ADCC 的调节发生倾斜，最终成为导致 HIV-1 相关免疫缺陷、失调和发病机制的新因素。因此，我们的数据首次提供了证据，表明在人类中，单核细胞作为 FcγRIII 介导的 NK 细胞功能的变阻器，维持着平衡的免疫反应。
