Ugolini S, Arpin C, Anfossi N, Walzer T, Cambiaggi A, Förster R, Lipp M, Toes R E, Melief C J, Marvel J, Vivier E
Centre d'Immunologie INSERM/CNRS de Marseille-Luminy, Case 906, 13288 Marseille, France.
Nat Immunol. 2001 May;2(5):430-5. doi: 10.1038/87740.
Inhibitory natural killer receptors (NKRs) such as killer cell immunoglobulin-like receptors (KIRs) in humans and Ly49 molecules in mice are expressed on NK cells and recognize multiple major histocompatibility (MHC) class I proteins. In humans and mice, a subset of CD8+ T cells also expresses NKRs and harbors a memory phenotype. Using mice that are transgenic for KIR2DL3 and its cognate HLA-Cw3 ligand, we show that engagement of inhibitory NKRs selectively drives the in vivo accumulation of a subset of memory-phenotype CD8+ T cells that express the beta chain of the interleukin 2 receptor. In vitro, recognition of MHC class I molecules by inhibitory NKRs on T cells down-regulated activation-induced cell death. These results unveil an MHC class I-dependent pathway that promotes the survival of a subset of memory-phenotype CD8+ T cells and also reveal an unexpected biological function for inhibitory NKRs on T cells.
抑制性自然杀伤受体（NKR），如人类的杀伤细胞免疫球蛋白样受体（KIR）和小鼠的Ly49分子，在自然杀伤细胞（NK细胞）上表达，并识别多种主要组织相容性复合体（MHC）I类蛋白。在人类和小鼠中，一部分CD8⁺ T细胞也表达NKR，并具有记忆表型。利用转染了KIR2DL3及其同源HLA - Cw3配体的转基因小鼠，我们发现抑制性NKR的结合选择性地驱动了一部分表达白细胞介素2受体β链的记忆表型CD8⁺ T细胞在体内的积累。在体外，T细胞上的抑制性NKR对MHC I类分子的识别下调了激活诱导的细胞死亡。这些结果揭示了一条依赖MHC I类分子的途径，该途径促进了一部分记忆表型CD8⁺ T细胞的存活，同时也揭示了T细胞上抑制性NKR意想不到的生物学功能。
