Rapid depletion of peripheral antigen-specific T cells in TCR-transgenic mice after oral administration of myelin basic protein

In myelin basic protein (MBP)-specific TCR-transgenic (Tg) mice, peripheral T cells express the V alpha2.3/V beta8.2-Tg TCR, demonstrate vigorous prol iferative responses to MBP in vitro, and can exhibit experimental autoimmun e encephalomyelitis (EAE) within 5 days of pertussis toxin injection. We ex plored the effects of oral administration of MBP on the cellular traffickin g of the MBP-specific TCR-Tg cells and the ability of oral MBP to protect T g mice from EAE. Tg mice were fed MBP, OVA or vehicle and sacrificed at var ious times after feeding. An immediate and dramatic decrease in V alpha2.3/ V beta8.2(+)-Tg cells was observed in the periphery within I h after feedin g. By 3 days after feeding, the percentage of Tg cells increased to near co ntrol levels, but decreased again by 10 days. When MBP or vehicle-fed Tg mi ce were challenged for EAE at this point, disease was severe in the vehicle -fed mice and reduced in the MBP-fed mice over the 40-day observation perio d. In vitro studies revealed a biphasic pattern of MBP proliferative unresp onsiveness and an induction of Th1 cytokines. Immunohistochemical staining showed that the number of Tg cells found in the intestinal lamina propria i ncreased dramatically as the number of Tg cells in the periphery decreased. There was no apparent proliferation of Tg cells in the lamina propria, ind icating that Tg cells trafficked there from the periphery. Taken together, these results suggest that T cell trafficking into the site of Ag depositio n acts to protect the TCR-Tg mouse from EAE.