Moalem G, Monsonego A, Shani Y, Cohen I R, Schwartz M
Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel Department of Immunology, The Weizmann Institute of Science, 76100 Rehovot, Israel.
FASEB J. 1999 Jul;13(10):1207-17. doi: 10.1096/fasebj.13.10.1207.
The central nervous system (CNS), unlike the peripheral nervous system (PNS), is an immune-privileged site in which local immune responses are restricted. Whereas immune privilege in the intact CNS has been studied intensively, little is known about its effects after trauma. In this study, we examined the influence of CNS immune privilege on T cell response to central nerve injury. Immunocytochemistry revealed a significantly greater accumulation of endogenous T cells in the injured rat sciatic nerve than in the injured rat optic nerve (representing PNS and CNS white matter trauma, respectively). Use of the in situ terminal deoxytransferase-catalyzed DNA nick end labeling (TUNEL) procedure revealed extensive death of accumulating T cells in injured CNS nerves as well as in CNS nerves of rats with acute experimental autoimmune encephalomyelitis, but not in injured PNS nerves. Although Fas ligand (FasL) protein was expressed in white matter tissue of both systems, it was more pronounced in the CNS. Expression of major histocompatibility complex (MHC) class II antigens was found to be constitutive in the PNS, but in the CNS was induced only after injury. Our findings suggest that the T cell response to central nerve injury is restricted by the reduced expression of MHC class II antigens, the pronounced FasL expression, and the elimination of infiltrating lymphocytes through cell death.
与外周神经系统(PNS)不同,中枢神经系统(CNS)是一个免疫特惠部位,局部免疫反应在其中受到限制。尽管完整中枢神经系统中的免疫特惠现象已得到深入研究,但对于创伤后的影响却知之甚少。在本研究中,我们研究了中枢神经系统免疫特惠对T细胞对中枢神经损伤反应的影响。免疫细胞化学显示,与损伤的大鼠视神经(分别代表外周神经系统和中枢神经系统白质创伤)相比,损伤的大鼠坐骨神经中内源性T细胞的积累明显更多。使用原位末端脱氧核苷酸转移酶介导的缺口末端标记(TUNEL)方法显示,在损伤的中枢神经系统神经以及患有急性实验性自身免疫性脑脊髓炎的大鼠的中枢神经系统神经中,积累的T细胞大量死亡,但在损伤的外周神经系统神经中则没有。尽管Fas配体(FasL)蛋白在两个系统的白质组织中均有表达,但在中枢神经系统中更为明显。发现主要组织相容性复合体(MHC)II类抗原在外周神经系统中组成性表达,但在中枢神经系统中仅在损伤后才被诱导表达。我们的研究结果表明,T细胞对中枢神经损伤的反应受到MHC II类抗原表达降低、FasL表达明显以及通过细胞死亡清除浸润淋巴细胞的限制。