Phagocytosis of apoptotic cells and cross-presentation by DC

自然杀伤细胞(NK细胞)通过与树突状细胞(DC)和T细胞相互作用，不仅参与先天免疫，还参与获得性免疫。所有被激活的人NK细胞都表达HLA-DR，并能启动MHCII依赖的CD4^+T细胞的增殖；然而，小鼠NK细胞表达MHCII的情况及其功能意义尚存争议。在这项研究中，我们发现NK-DC相互作用导致MHCII阳性NK细胞的出现。在体外或体内激活后，小鼠常规NK细胞不能诱导MHCII转录本，但能迅速从DC获得MHCII蛋白。MHCIIH2-ab1缺陷的NK细胞过继转移到野生型(WT)小鼠体内或与WT脾树突状细胞共同培养后，I-Ab阳性。MHCII的NK获得是通过称为巨噬细胞增多症的细胞间膜转移介导的，而不是通过DAP10/12和MHCI结合的NK细胞受体信号介导的。MHCII修饰的NK细胞同时从DC获得CD80和CD86等费用模拟分子，但其表达水平尚未达到功能水平。因此，MHCII修饰的NK细胞抑制DC诱导的CD4^+T细胞反应，而不是通过竞争性抗原提呈激活CD4^+T细胞。在迟发性超敏反应的小鼠模型中，过继转移MHCII修饰的NK细胞可以减轻足垫肿胀。这些结果表明，通过NK-DC相互作用产生的MHCII修饰的NK细胞调节T细胞介导的免疫应答。

N atural killer (NK)cells contribute to not only innate but also adaptive immunity by interacting with dendritic cells (DCs)and T cells. All activated human NK cells express HLA-DR and can initiate MHCII-dependent CD4^+ T cell proliferation ; however, the expression of MHCII by mouse NK cells and its functional significance are controversial. In this study, we show that NK-DC interactions result in the emergence of MHCII-positive NK cells. Upon in vitro or in vivo activation, mouse conventional NK cells did not induce MHCII transcripts, but rapidly acquired MHCII protein from DCs. MHCII H2-Ab1-deficient NK cells turned I-A b-positive when adoptively transferred into wild type (WT)mice or when cultured with WT splenic DCs. NK acquisition of MHCII was mediated by intercellular membrane transfer called trogocytosis, but not upon DAP10/12 and MHCI-binding NK cell receptor signaling. MHCII-dressed NK cells concurrently acquired cost imulatory molecules such as CD80 and CD86 from DCs ; however, their expression did not reach functional levels. Therefore, MHCII-dressed NK cells inhibited DC-induced CD4^+ T cell responses rather than activated CD4^+ T cells by competitive antigen presentat ion. In a mouse model for delayed-type hypersensitivity, adoptive transfer of MHCII-dressed NK cells attenuated the footpad swelling. These results suggest that MHCII-dressed NK cells generated through NK-DC interactions regulate T cell-mediated immune r esponses.