Cutting edge: RANTES regulates Fas ligand expression and killing by HIV-specific CD8 cytotoxic T cells

Based on the previous observation that RANTES mediates the cytotoxic activi ty of human HIV-specific CD8(+) T cells via the chemokine receptor CCR3, we studied the effect of this chemokine on different effector CD8(+) cytolyti c cells requiring Fas/Fas ligand (FasL) or perforin-dependent pathway,In CT Ls derived from PBMCs of HIV-infected patients, both the spontaneous and th e RANTES-induced cytotoxicity were inhibited by anti-FasL, neutralizing Abs , In contrast, allogeneic CTLs or NK cells killing through perforin were no t affected by RANTES and anti-Fast Ab, Accordingly, RANTES enhanced the exp ression of Fast in a concentration- and time-dependent manner in HIV-specif ic CTLs, whereas anti-RANTES Ab decreased markedly Fast expression. Finally , cell surface expression of Fast protein in HIV-specific CTLs was also upr egulated by eotaxin, a selective ligand for CCR3, Our observations show tha t the action of RANTES via CCR3 is necessary to regulate Fast expression on HIV-specific CD8(+) T cells that kill through the Fas/FasL, pathway.