CD16- natural killer cells: enrichment in mucosal and secondary lymphoid tissues and altered function during chronic SIV infection
CD16- natural killer cells: enrichment in mucosal and secondary lymphoid tissues and altered function during chronic SIV infection
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DOI：
10.1182/blood-2010-01-265595
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发表时间：
2010-06-03
期刊：
影响因子：
20.3
通讯作者：
Johnson, R. Paul
中科院分区：
文献类型：
--
作者：
Reeves, R. Keith;Gillis, Jacqueline;Johnson, R. Paul
自然杀伤（NK）细胞有助于控制HIV/SIV感染。我们根据CD 56和CD 16的表达定义了猕猴NK细胞亚群，发现它们的分布是高度不同的。CD 16（+）NK细胞在外周血中占主导地位，而大多数粘膜NK细胞为CD 56（+），淋巴结含有CD 56（+）和CD 16（-）CD 56（-）（双阴性[DN]）亚群。在亚群中，功能特征也不同，CD 16（+）NK细胞表达高水平的细胞溶解分子，CD 56（+）NK细胞主要是精氨酸分泌细胞，而DN NK细胞具有这两种功能。在SIV慢性感染的猕猴中，循环中的CD 16（+）和DN NK细胞数量增加，尽管细胞毒性标志物增加，但细胞因子分泌减少。值得注意的是，SIV感染动物的CD 56（+）NK细胞上调穿孔素、颗粒酶B和CD 107 a。相比之下，淋巴结归巢分子CD 62配体（CD 62 L）和C-C趋化因子受体7型（CCR 7），主要表达在CD 56（+）和DN NK细胞上，在感染动物的NK细胞上显著下调。这些数据表明，SIV感染驱动NK细胞功能的转变，其特征在于细胞因子产生减少，细胞毒性增加，以及从次级淋巴器官中运输，这表明NK细胞库不仅是异质的，而且是可塑的。（血。2010; 115（22）：4439-4446）
Natural killer (NK) cells contribute to control of HIV/SIV infection. We defined macaque NK-cell subsets based on expression of CD56 and CD16 and found their distribution to be highly disparate. CD16(+) NK cells predominated in peripheral blood, whereas most mucosal NK cells were CD56(+), and lymph nodes contained both CD56(+) and CD16(-)CD56(-) (double-negative [DN]) subsets. Functional profiles were also distinct among subsets CD16(+) NK cells expressed high levels of cytolytic molecules, and CD56(+) NK cells were predominantly cytokine-secreting cells, whereas DN NK possessed both functions. In macaques chronically infected with SIV, circulating CD16(+) and DN NK cells were expanded in number and, although markers of cytoxicity increased, cytokine secretion decreased. Notably, CD56(+) NK cells in SIV-infected animals up-regulated perforin, granzyme B, and CD107a. In contrast, the lymph node homing molecules CD62 ligand (CD62L) and C-C chemokine receptor type 7 (CCR7), which are expressed primarily on CD56(+) and DN NK cells, were significantly down-regulated on NK cells from infected animals. These data demonstrate that SIV infection drives a shift in NK-cell function characterized by decreased cytokine production, expanded cytotoxicity, and trafficking away from secondary lymphoid organs, suggesting that the NK-cell repertoire is not only heterogeneous but also plastic. (Blood. 2010; 115(22): 4439-4446)