Hadida F, Vieillard V, Mollet L, Clark-Lewis I, Baggiolini M, Debré P
Laboratoire d'Immunologie Cellulaire, Unité Mixte de Recherche 7627, Centre National de la Recherche Scientifique Bâtiment CERVI, Hôpital Pitié-Salpétrière, Paris, France.
J Immunol. 1999 Aug 1;163(3):1105-9.
Based on the previous observation that RANTES mediates the cytotoxic activity of human HIV-specific CD8+ T cells via the chemokine receptor CCR3, we studied the effect of this chemokine on different effector CD8+ cytolytic cells requiring Fas/Fas ligand (FasL) or perforin-dependent pathway. In CTLs derived from PBMCs of HIV-infected patients, both the spontaneous and the RANTES-induced cytotoxicity were inhibited by anti-FasL neutralizing Abs. In contrast, allogeneic CTLs or NK cells killing through perforin were not affected by RANTES and anti-FasL Ab. Accordingly, RANTES enhanced the expression of FasL in a concentration- and time-dependent manner in HIV-specific CTLs, whereas anti-RANTES Ab decreased markedly FasL expression. Finally, cell surface expression of FasL protein in HIV-specific CTLs was also up-regulated by eotaxin, a selective ligand for CCR3. Our observations show that the action of RANTES via CCR3 is necessary to regulate FasL expression on HIV-specific CD8+ T cells that kill through the Fas/FasL pathway.
基于之前的观察结果，即RANTES通过趋化因子受体CCR3介导人类HIV特异性CD8+ T细胞的细胞毒性活性，我们研究了这种趋化因子对不同效应性CD8+ 溶细胞性细胞的影响，这些细胞需要Fas/Fas配体（FasL）或穿孔素依赖性途径。在源自HIV感染患者外周血单核细胞（PBMC）的细胞毒性T淋巴细胞（CTL）中，抗FasL中和抗体抑制了自发的和RANTES诱导的细胞毒性。相反，通过穿孔素进行杀伤的同种异体CTL或自然杀伤（NK）细胞不受RANTES和抗FasL抗体的影响。因此，RANTES以浓度和时间依赖性方式增强了HIV特异性CTL中FasL的表达，而抗RANTES抗体则显著降低了FasL的表达。最后，嗜酸性粒细胞趋化因子（一种CCR3的选择性配体）也上调了HIV特异性CTL中FasL蛋白的细胞表面表达。我们的观察结果表明，RANTES通过CCR3的作用对于调节通过Fas/FasL途径杀伤的HIV特异性CD8+ T细胞上FasL的表达是必要的。
