Cutting edge: The NK cell receptor 2B4 augments antigen-speciflic T cell cytotoxicity through CD48 ligation on neighboring T cells

Cutting edge: The NK cell receptor 2B4 augments antigen-speciflic T cell cytotoxicity through CD48 ligation on neighboring T cells
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DOI:
10.4049/jimmunol.170.10.4881
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发表时间:
2003-05-15
影响因子:
4.4
通讯作者:
Kumar, V
Kumar, V
中科院分区:
医学2区
文献类型:
--
作者:
Lee, KM;Bhawan, S;Kumar, V

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2B4在所有NK细胞和部分记忆/效应CD8(+)T细胞上表达。2B4与CD48结合并激活NK细胞毒作用,但其对CD8+T细胞的作用尚不清楚。此外,2B4的两种亚型(2B4S和2B4L)存在于小鼠体内,但各亚型的作用尚不清楚。为了解决这些问题,我们从L-d特异的2C/Rag2(-/-)TCR转基因小鼠中制备了原代T细胞培养物,并将2B4S或2B4L转导给它们。2B4S或2B4L转导的T细胞对CD48(+)和CD48-靶细胞的杀伤活性明显高于对照细胞,提示CD48不需要将2B4连接到靶细胞上,从而发挥2B4的功能。相反,2B4/CD48在相邻T细胞上的相互作用似乎是细胞毒性的关键。因此,2B4在MHC限制性细胞毒中作为CD8(+)T细胞的共刺激因子发挥作用。我们得出结论,T细胞之间的2B4/CD48相互作用可以增强其特异性靶点的CTL裂解。
2B4 is expressed on all NK and a subset of memory/effector CD8(+) T cells. 2B4 binds to CD48 and activates NK cytotoxicity, but its function on CD8(+) T cells is not clear. Furthermore, two isoforms of 2B4 (2B4S and 2B4L) exist in mice but the role of individual isoforms is not known. To address these questions, we generated primary T cell cultures from L-d-specific 2C/Rag2(-/-) TCR transgenic mice and transduced them with 2B4S or 2B4L. 2B4S- or 2B4L-transduced T cells showed greater cytotoxicity over control cells against CD48(+) and CD48- targets, suggesting that ligation of 2B4 by CD48 on target cells was not necessary,for 2B4 function. Rather, 2B4/CD48 interaction on adjacent T cells appeared to be critical for cytotoxicity. Therefore, 2B4 functions as a costimulator of CD8(+) T cells in MHC-restricted cytotoxicity. We conclude that 2B4/CD48 interactions among T cells themselves can augment CTL lysis of their specific targets.