在通过接种髓鞘碱性蛋白诱导Lewis大鼠发生实验性自身免疫性脑脊髓炎后恢复过程中，脊髓中Vβ8.2 + T淋巴细胞的凋亡。

Apoptosis of V beta 8.2+ T lymphocytes in the spinal cord during recovery from experimental autoimmune encephalomyelitis induced in Lewis rats by inoculation with myelin basic protein.

作者信息

McCombe P A, Nickson I, Tabi Z, Pender M P

机构信息

Department of Medicine, University of Queensland, Royal Brisbane Hospital, Herston, Australia.

出版信息

J Neurol Sci. 1996 Jul;139(1):1-6.

PMID:8836965

Abstract

To study T cell apoptosis during spontaneous recovery from experimental autoimmune encephalomyelitis (EAE), we extracted lymphocytes from the spinal cords of Lewis rats with EAE induced by inoculation with myelin basic protein (MBP) and adjuvants. Using flow cytometry we assessed the numbers of CD5+ and TCR alpha beta + lymphocytes, as well as V beta 8.2+ lymphocytes, which constitute the predominant encephalitogenic MBP-reactive cells in Lewis rats. Rats developed neurological signs of disease 10-12 days after inoculation. The peak of disease was on day 14 after inoculation and was followed by clinical recovery. The numbers of CD5+, TCR alpha beta + and V beta 8.2+ cells obtained from the spinal cord were greatest on day 13. During spontaneous clinical recovery, there was a decline in the numbers of all the cells studied, with a selective loss of V beta 8.2+ cells from the CD5+ and TCR alpha beta + populations. To determine whether the decline in lymphocyte numbers was due to apoptosis, we used simultaneous surface labelling and propidium iodide staining of the DNA of the cells extracted from the spinal cord. From day 14 onwards, there was selective enrichment of V beta 8.2+ cells in the apoptotic population, and the percentage of V beta 8.2+ cells undergoing apoptosis was greater than the percentages of CD5+ and TCR alpha beta + cells undergoing apoptosis. These findings indicate that recovery from acute EAE is associated with the selective apoptosis, in the central nervous system, of these disease-relevant cells. The findings in this study of actively induced EAE are similar to those of our previous study of EAE induced by transfer of encephalitogenic MBP-specific T cells (Z. Tabi et al., Eur. J. Immunol. 24: 2609-2617, 1994) and further support the hypothesis that selective apoptosis of autoreactive T cells in the central nervous system is of primary importance in spontaneous recovery from EAE.

摘要

为研究实验性自身免疫性脑脊髓炎（EAE）自然恢复过程中的T细胞凋亡，我们从接种髓鞘碱性蛋白（MBP）和佐剂诱导EAE的Lewis大鼠脊髓中提取淋巴细胞。使用流式细胞术，我们评估了CD5⁺和TCRαβ⁺淋巴细胞以及Vβ8.2⁺淋巴细胞的数量，这些细胞构成Lewis大鼠中主要的致脑炎性MBP反应性细胞。大鼠在接种后10 - 12天出现疾病的神经学体征。疾病高峰在接种后第14天，随后临床恢复。从脊髓获得的CD5⁺、TCRαβ⁺和Vβ8.2⁺细胞数量在第13天最多。在自然临床恢复过程中，所有研究细胞的数量均下降，CD5⁺和TCRαβ⁺群体中的Vβ8.2⁺细胞选择性丢失。为确定淋巴细胞数量的下降是否由于凋亡，我们对从脊髓提取的细胞进行DNA的同步表面标记和碘化丙啶染色。从第14天起，凋亡群体中Vβ8.2⁺细胞选择性富集，且发生凋亡的Vβ8.2⁺细胞百分比大于发生凋亡的CD5⁺和TCRαβ⁺细胞百分比。这些发现表明急性EAE的恢复与中枢神经系统中这些疾病相关细胞的选择性凋亡有关。本研究中主动诱导EAE的结果与我们先前关于致脑炎性MBP特异性T细胞转移诱导EAE的研究结果相似（Z. Tabi等人，《欧洲免疫学杂志》24: 2609 - 2617，1994），进一步支持了以下假说：中枢神经系统中自身反应性T细胞的选择性凋亡在EAE的自然恢复中至关重要。