Song Fei, Wardrop Richard M, Gienapp Ingrid E, Stuckman Scott S, Meyer Abbie L, Shawler Todd, Whitacre Caroline C
Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University College of Medicine and Public Health, 760 Biomedical Research Tower, 460 West 12th Avenue, Columbus, OH 43210, USA.
J Autoimmun. 2008 Jun;30(4):230-7. doi: 10.1016/j.jaut.2007.10.002. Epub 2007 Nov 14.
Expression of MCP-1 in the central nervous system (CNS) is associated with various neuroinflammatory diseases, including multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). In this study, we found that MCP-1 was decreased in the CNS but increased in the gut following oral administration of myelin basic protein (MBP) correlating with protection from EAE. To study the trafficking and the fate of T cells during oral tolerance, MBP-specific TCR transgenic (Tg) CD4(+) T cells were labeled using 5,6-carboxy-succinimidyl-fluorescein-ester (CFSE) and transferred intravenously to syngeneic B10.PL recipients before feeding with either MBP or PBS. We observed that the CFSE-labeled T cells traffic to the peripheral lymphoid tissue and the Peyer's patches (PP). The labeled T cells proliferate in vivo in both the lymph node and the PP 48h after MBP feeding, but the cells are maintained in the PP longer than in the LN. CFSE-labeled cells in the PP have high levels of CD69 and Fas expression which is accompanied by increased apoptosis after MBP feeding. Our observations suggest that oral administration of autoantigen induces an elevation of MCP-1 in the gut, early T cell trafficking and activation in the periphery and the PP, followed by deletion of autoreactive T cells in the PP.
单核细胞趋化蛋白-1（MCP-1）在中枢神经系统（CNS）中的表达与多种神经炎症性疾病相关，包括多发性硬化症（MS）和实验性自身免疫性脑脊髓炎（EAE）。在本研究中，我们发现口服髓鞘碱性蛋白（MBP）后，CNS中MCP-1水平降低，但肠道中MCP-1水平升高，这与对EAE的保护作用相关。为了研究口服耐受过程中T细胞的迁移和命运，在给同基因B10.PL受体喂食MBP或PBS之前，使用5,6-羧基-琥珀酰亚胺基-荧光素酯（CFSE）标记MBP特异性TCR转基因（Tg）CD4(+) T细胞，并将其静脉注射到受体体内。我们观察到CFSE标记的T细胞迁移至外周淋巴组织和派氏结（PP）。喂食MBP 48小时后，标记的T细胞在淋巴结和PP中均在体内增殖，但细胞在PP中的存留时间比在淋巴结中更长。PP中CFSE标记的细胞具有高水平的CD69和Fas表达，喂食MBP后细胞凋亡增加。我们的观察结果表明，口服自身抗原会诱导肠道中MCP-1升高，早期T细胞在外周和PP中迁移和活化，随后PP中的自身反应性T细胞被清除。
