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Abstract

Myelin-specific, pro-inflammatory T(H)17 cells are widely regarded as the drivers of experimental autoimmune encephalomyelitis (EAE), an animal model for Multiple sclerosis (MS). The factors, responsible for the generation and maintenance of T(H)17 cells as well as their participation in the pathogenic cascade leading to the demyelinating disease, have been studied extensively. However, how these harmful autoreactive cells are controlled in vivo remains unclear. By comparing TCR transgenic mice on a disease susceptible and a disease resistant genetic background, we show here that pathogenic T(H)17 cells are sequestered within the intestine of spontaneous EAE resistant B10.S mice. Disease resistant B10.S mice harbored higher frequencies of T(H)17 cells in the intestine compared to EAE susceptible SJL/J mice. Moreover, transferred T(H)17 cells selectively migrated to intestinal lymphoid organs of B10.S mice. The sequestration of T(H)17 cells in the gut was partially dependent on the gut homing receptor alpha 4 beta 7-mediated adhesion to the intestine. Administration of alpha 4 beta 7 blocking-antibodies increased the peripheral availability of T(H)17 cells, resulting in increased EAE severity after immunization in B10.S mice. Together, these results support the concept that the intestine is a check-point for controlling pathogenic, organ-specific T cells.