IL-2-activated CD8+ CD44high cells express both adaptive and innate immune system receptors and demonstrate specificity for syngeneic tumor cells

IL-2-activated CD8+ CD44high cells express both adaptive and innate immune system receptors and demonstrate specificity for syngeneic tumor cells
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DOI:
10.4049/jimmunol.171.7.3442
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发表时间:
2003-10-01
影响因子:
4.4
通讯作者:
Teh, HS
Teh, HS
中科院分区:
医学2区
文献类型:
--
作者:
Dhanji, S;Teh, HS

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CD 8(+)T细胞依赖于α TCR进行Ag识别和功能。然而,Ag激活的CD 8(+)T细胞也可以表达先天免疫系统的受体。在这项研究中,我们检测了正常小鼠中表达高水平CD 44的CD 8(+)T细胞(CD 8(+)CD 44高细胞)群体上NK受体的表达。这些细胞与传统的记忆性CD 8(+)T细胞不同,它们通过CD 48/CD 2依赖性机制增殖并响应IL 2而被激活。在活化前,它们表达低水平或不可检测水平的NK受体,但在用IL-2活化后,它们表达显著水平的活化NK受体,包括2B 4和NKG 2D。有趣的是,IL-2激活的细胞在杀死同源肿瘤细胞方面表现出偏好。通过靶细胞上NKG 2D配体Rae-1的表达,这种对同源肿瘤细胞的杀伤作用大大增强。与传统的CD 8 + T细胞相反,IL-2激活的CD 8(+)CD 44(高)细胞表达DAP 12,这是一种通常在激活的NK细胞中表达的衔接分子。这些观察结果表明,活化的CD 8(+)CD 44(高)细胞表达适应性和先天性免疫系统的受体,并可能在监视已被感染或转化改变的宿主细胞中发挥独特的作用。
CD8(+) T cells depend on the alphabeta TCR for Ag recognition and function. However, Ag-activated CD8(+) T cells can also express receptors of the innate immune system. In this study, we examined the expression of NK receptors on a population of CD8(+) T cells expressing high levels of CD44 (CD8(+)CD44 high Cells) from normal mice. These cells are distinct from conventional memory CD8(+) T cells and they proliferate and become activated in response to IL 2 via a CD48/CD2-dependent mechanism. Before activation, they express low or undetectable levels of NK receptors but upon activation with IL-2 they expressed significant levels of activating NK receptors including 2B4 and NKG2D. Interestingly, the IL-2-activated cells demonstrate a preference in the killing of syngeneic tumor cells. This killing of syngeneic tumor cells was greatly enhanced by the expression of the NKG2D ligand Rae-1 on the target cell. In contrast to conventional CD8+ T cells, IL-2-activated CD8(+)CD44(high) cells express DAP12, an adaptor molecule that is normally expressed in activated NK cells. These observations indicate that activated CD8(+)CD44(high) cells express receptors of both the adaptive and innate immune system and may play a unique role in the surveillance of host cells that have been altered by infection or transformation.