A novel function-associated molecule related to non-MHC-restricted cytotoxicity mediated by activated natural killer cells and T cells.

A novel function-associated molecule related to non-MHC-restricted cytotoxicity mediated by activated natural killer cells and T cells.
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DOI:
10.4049/jimmunol.151.1.60
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发表时间:
1993-07
影响因子:
4.4
通讯作者:
B. Garni-Wagner;A. Purohit;P. A. Mathew;M. Bennett;V. Kumar
B. Garni-Wagner;A. Purohit;P. A. Mathew;M. Bennett;V. Kumar
中科院分区:
医学2区
文献类型:
--
作者:
B. Garni-Wagner;A. Purohit;P. A. Mathew;M. Bennett;V. Kumar

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NK细胞和IL-2增殖的脾T细胞介导非MHC限制性细胞毒性。参与这一过程的分子还没有很好的定义。我们描述了一种新的66-kDa的细胞表面分子称为2B 4,是介导非MHC限制性细胞毒性的细胞上表达。所有静息和rIL-2培养的NK细胞以及在高剂量rIL-2中培养的大量T细胞均为2B 4+。在新鲜和培养的脾细胞中,所有非MHC限制性细胞毒性均包含在2B 4+细胞群中。除了定义能够非MHC限制性杀伤的细胞外,2B 4分子还参与调节其功能。在存在抗2B 4抗体的情况下,培养的NK细胞和非MHC限制性T细胞对多种FcR-和FcR+靶标的裂解活性大大增强。抗2B 4抗体还能够抑制IL-2激活的NK细胞中的其他信号,如IFN-γ分泌和颗粒胞吐。此外,2B 4 + T细胞可特异性裂解2B 4杂交瘤细胞。与许多其他活化和粘附分子(如鼠CD 2、LFA-1和CD 16)不同,2B 4的表达仅限于介导NK样杀伤的细胞。相反,不表达2B 4的高度活化的T细胞不介导非MHC限制性杀伤。总之,这些数据表明,2B 4分子可能是介导非MHC限制性杀伤的细胞上受体复合物的一部分或信号转导复合物的组分。
NK cells and IL-2-propagated splenic T cells mediate non-MHC-restricted cytotoxicity. The molecules involved in this process are not well defined. We describe a novel 66-kDa cell surface molecule called 2B4 that is expressed on cells that mediate non-MHC-restricted cytotoxicity. All resting and rIL-2 cultured NK cells and a significant number of T cells cultured in high doses of rIL-2 are 2B4+. In fresh as well as cultured spleen cells, all non-MHC-restricted cytotoxicity is contained within the 2B4+ population. In addition to defining cells capable of non-MHC-restricted killing, the 2B4 molecule is also involved in modulation of their function. In the presence of anti-2B4, the lytic activity of cultured NK cells and non-MHC-restricted T cells against a wide variety of FcR- and FcR+ targets is greatly augmented. Anti-2B4 is also able to transduce other signals in IL-2-activated NK cells such as IFN-gamma secretion and granule exocytosis. In addition, 2B4+ T cells can specifically lyse the 2B4 hybridoma cells. Unlike many other activation and adhesion molecules (such as murine CD2, LFA-1, and CD16), 2B4 expression is restricted to cells that mediate NK-like killing. Conversely, highly activated T cells that do not express 2B4 do not mediate non-MHC-restricted killing. Together these data suggest that the 2B4 molecule is likely to be a part of a receptor complex or a component of signal-transducing complex on cells that mediate non-MHC-restricted killing.