Kojima H, Eshima K, Takayama H, Sitkovsky M V
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 1997 Sep 15;159(6):2728-34.
Exquisite specificity toward Ag-bearing cells (cognate targets) is one of the most important properties of CD8+ CTL-mediated cytotoxicity. Using highly Ag-specific CD8+ CTL lines and clones, which spare noncognate, Ag-free targets, we found that in the presence of Ag-bearing targets the CTL acquire the ability to lyse noncognate target cells (bystanders). It is shown that the unexpectedly rapid and efficient lysis of bystanders by Ag-activated CTL is mediated by a Fas ligand (FasL)/Fas-based mechanism and does not depend on perforin. The CTL lysed Fas-expressing bystanders, but spared the Fas-negative or anti-Fas mAb-resistant bystander cells. Accordingly, the FasL-deficient gld/gld CTL did not kill bystanders, while perforin-deficient CTL did. Unlike anti-Fas mAb-induced cell death, the lysis of bystanders was not only FasL/Fas dependent but also required adhesion molecule LFA-1 on the surface of the activated CTL. Lysis of bystanders is viewed as acceptable "collateral" damage, but the persistent presence of activated CTL could result in immunopathologies involving functional Fas-expressing tissues.
对携带抗原的细胞（同源靶细胞）的高度特异性是CD8 + 细胞毒性T淋巴细胞（CTL）介导的细胞毒性最重要的特性之一。使用高度抗原特异性的CD8 + CTL系和克隆，这些细胞对非同源、无抗原的靶细胞无损伤作用，我们发现，在存在携带抗原的靶细胞时，CTL获得了裂解非同源靶细胞（旁观者细胞）的能力。结果表明，抗原激活的CTL对旁观者细胞的意外快速且高效的裂解是由基于Fas配体（FasL）/Fas的机制介导的，且不依赖穿孔素。CTL裂解表达Fas的旁观者细胞，但对Fas阴性或抗Fas单克隆抗体耐药的旁观者细胞无损伤作用。因此，FasL缺陷的gld/gld CTL不会杀伤旁观者细胞，而穿孔素缺陷的CTL则会。与抗Fas单克隆抗体诱导的细胞死亡不同，旁观者细胞的裂解不仅依赖FasL/Fas，还需要活化的CTL表面的黏附分子LFA-1。旁观者细胞的裂解被视为可接受的“附带”损伤，但活化的CTL持续存在可能导致涉及表达功能性Fas的组织的免疫病理学。
