CD56brightPerforinlow Noncytotoxic Human NK Cells Are Abundant in Both Healthy and Neoplastic Solid Tissues and Recirculate to Secondary Lymphoid Organs via Afferent Lymph
CD56brightPerforinlow Noncytotoxic Human NK Cells Are Abundant in Both Healthy and Neoplastic Solid Tissues and Recirculate to Secondary Lymphoid Organs via Afferent Lymph
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DOI：
10.4049/jimmunol.1301889
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发表时间：
2014-04-15
影响因子：
4.4
通讯作者：
Ferlazzo, Guido
中科院分区：
文献类型：
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作者：
Carrega, Paolo;Bonaccorsi, Irene;Ferlazzo, Guido
由于有关 NK 细胞在实体器官中的分布和运输的信息有限，我们分析了来自不同人体部位的各种组织。 NK 细胞广泛分布在大多数实体组织中，尽管它们的数量根据分析的组织/器官的不同而有很大差异。有趣的是，这种分布似乎是子集特异性的，因为一些组织优先由 CD56（亮）穿孔素（低）NK 细胞填充，而其他组织则优先由 CD56（暗）穿孔素（高）细胞毒性对应物填充。然而，大多数组织高度富集CD56(bright)perforin(low)细胞，并且NK亚群的分布与趋化因子的组织基因表达一致，其受体在两个亚群中表现不同。值得注意的是，肿瘤转化后组织的趋化因子表达模式发生了改变。因此，尽管恶性转化时浸润组织的 NK 细胞总量没有显着变化，但浸润组织的 NK 亚群的相对比例有所不同，有富含非细胞毒性细胞的肿瘤浸润 NK 群体的趋势。除实体组织外，血清液中还检测到CD56（亮）穿孔素（低）NK细胞，这代表人类传入淋巴的累积，表明它们可能离开外周实体组织并通过淋巴管再循环至次级淋巴器官。我们的结果提供了人体组织中 NK 细胞的全面图谱，证明离散的 NK 子集在大多数人体组织中填充和再循环，并且器官特异性趋化因子表达模式可能会影响它们的分布。在这种情况下，肿瘤转化时的趋化因子开关可能代表了肿瘤免疫逃逸的一种新机制。
As limited information is available regarding the distribution and trafficking of NK cells among solid organs, we have analyzed a wide array of tissues derived from different human compartments. NK cells were widely distributed in most solid tissues, although their amount varied significantly depending on the tissue/ organ analyzed. Interestingly, the distribution appeared to be subset specific, as some tissues were preferentially populated by CD56(bright)perforin(low) NK cells, with others by the CD56(dim)perforin(high) cytotoxic counterpart. Nevertheless, most tissues were highly enriched in CD56(bright)perforin(low) cells, and the distribution of NK subsets appeared in accordance with tissue gene expression of chemotactic factors, for which receptors are differently represented in the two subsets. Remarkably, chemokine expression pattern of tissues was modified after neoplastic transformation. As a result, although the total amount of NK cells infiltrating the tissues did not significantly change upon malignant transformation, the relative proportion of NK subsets infiltrating the tissues was different, with a trend toward a tumor-infiltrating NK population enriched in noncytotoxic cells. Besides solid tissues, CD56(bright)perforin(low) NK cells were also detected in seroma fluids, which represents an accrual of human afferent lymph, indicating that they may leave peripheral solid tissues and recirculate to secondary lymphoid organs via lymphatic vessels. Our results provide a comprehensive mapping of NK cells in human tissues, demonstrating that discrete NK subsets populate and recirculate through most human tissues and that organ-specific chemokine expression patterns might affect their distribution. In this context, chemokine switch upon neoplastic transformation might represent a novel mechanism of tumor immune escape.