Kishimoto H, Surh C D, Sprent J
Department of Immunology, IMM4, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
J Exp Med. 1998 May 4;187(9):1427-38. doi: 10.1084/jem.187.9.1427.
To seek information on the role of Fas in negative selection, we examined subsets of thymocytes from normal neonatal mice versus Fas-deficient lpr/lpr mice injected with graded doses of antigen. In normal mice, injection of 1-100 microg of staphylococcal enterotoxin B (SEB) induced clonal elimination of SEB-reactive Vbeta8+ cells at the level of the semi-mature population of HSAhi CD4+ 8- cells found in the thymic medulla; deletion of CD4+ 8+ cells was minimal. SEB injection also caused marked elimination of Vbeta8+ HSAhi CD4+ 8- thymocytes in lpr/lpr mice. Paradoxically, however, elimination of these cells in lpr/lpr mice was induced by low-to-moderate doses of SEB (</=1 microg) but not by high doses (100 microg). Similar findings applied when T cell receptor transgenic mice were injected with specific peptide. These findings suggest that clonal elimination of semi-mature medullary T cells is Fas independent at low doses of antigen but Fas dependent at high doses. Previous reports documenting that negative selection is not obviously impaired in lpr/lpr mice could thus reflect that the antigens studied were expressed at only a low level.
为了探寻Fas在阴性选择中的作用，我们检测了正常新生小鼠与注射了不同剂量抗原的Fas缺陷型lpr/lpr小鼠的胸腺细胞亚群。在正常小鼠中，注射1 - 100微克葡萄球菌肠毒素B（SEB）可诱导胸腺髓质中半成熟的HSAhi CD4+ 8-细胞水平的SEB反应性Vbeta8+细胞发生克隆清除；CD4+ 8+细胞的清除极少。SEB注射也导致lpr/lpr小鼠中Vbeta8+ HSAhi CD4+ 8-胸腺细胞显著清除。然而，矛盾的是，lpr/lpr小鼠中这些细胞的清除是由低至中等剂量的SEB（≤1微克）诱导的，而不是高剂量（100微克）。当给T细胞受体转基因小鼠注射特异性肽时也有类似发现。这些发现表明，低剂量抗原时半成熟髓质T细胞的克隆清除不依赖Fas，但高剂量时依赖Fas。先前记录lpr/lpr小鼠阴性选择未明显受损的报告因此可能反映所研究的抗原仅以低水平表达。
