Garni-Wagner B A, Purohit A, Mathew P A, Bennett M, Kumar V
Graduate Program in Immunology, University of Texas Southwestern Medical Center, Dallas 75235.
J Immunol. 1993 Jul 1;151(1):60-70.
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.
自然杀伤（NK）细胞和白细胞介素-2（IL-2）扩增的脾T细胞介导非主要组织相容性复合体（MHC）限制的细胞毒性。参与这一过程的分子尚未完全明确。我们描述了一种名为2B4的新型66 kDa细胞表面分子，它在介导非MHC限制细胞毒性的细胞上表达。所有静息和经重组白细胞介素-2（rIL-2）培养的NK细胞以及大量在高剂量rIL-2中培养的T细胞均为2B4阳性。在新鲜以及培养的脾细胞中，所有非MHC限制的细胞毒性都存在于2B4阳性群体中。除了确定能够进行非MHC限制杀伤的细胞外，2B4分子还参与调节它们的功能。在抗2B4存在的情况下，培养的NK细胞和非MHC限制的T细胞对多种Fc受体阳性（FcR+）和Fc受体阴性（FcR-）靶标的裂解活性会大大增强。抗2B4还能够在IL-2激活的NK细胞中传导其他信号，如γ干扰素（IFN-γ）分泌和颗粒胞吐作用。此外，2B4阳性T细胞能够特异性裂解2B4杂交瘤细胞。与许多其他激活和黏附分子（如小鼠CD2、淋巴细胞功能相关抗原-1（LFA-1）和CD16）不同，2B4的表达仅限于介导自然杀伤样杀伤的细胞。相反，不表达2B4的高度激活的T细胞不介导非MHC限制的杀伤。这些数据共同表明，2B4分子可能是介导非MHC限制杀伤的细胞上受体复合物的一部分或信号转导复合物的一个组成部分。
