Gastrointestinal tract is the place where encephalitogenic T cells develop in the spontaneous EAE mice (101.11)

Abstract

Abstract Multiple sclerosis (MS) is an autoimmune disease exhibiting features of demeylination and axonal loss in the central nervous system (CNS). Although CNS-specific Th1 and Th17 cells have been suggested to initiate the disease, it is still unknown how these effector T cells develop in MS patients. To address this question, we have generated transgenic mice that express T cell receptor (TCR) genes specific for myelin basic protein (MBP) and HLA-DR2a genes that were isolated from an MS patient. The humanized MBP-TCR Tg mice developed spontaneous EAE. Interestingly Th1 and Th17 cells developed in the mesenteric lymph nodes and the colon more efficiently than in other lymphoid organs in the spontaneous EAE mice, and their development was much lower in the gastrointestinal (GI) tract of healthy MBP-TCR Tg mice. This data suggests that MBP-specific T cells differentiate into Th1 and Th17 encephalitogenic T cells in the colon and migrate into the CNS from mesenteric lymph nodes. Alternatively, MBP-specific Th1 and Th17 encephalitogenic T cells develop in the other lymphoid organs and preferentially migrate into the gut. Interestingly, CD4 T cells infiltrates in the CNS of spontaneous EAE mice expressed gut-homing receptors in addition to CNS-homing receptors. These data suggest that the GI-tract may be an important site for the differentiation of encephalitogenic T cells in spontaneous EAE mice.