Retention of autoreactive CD4+ recent thymic emigrants in the liver (BA8P.127)

Abstract

Abstract T cells escape from negative selection in the thymus require peripheral tolerance enforcement to prevent them from triggering T cell-mediated autoimmunity. Using adoptive transfer model and RAG2p-GFP transgenic mouse system, we demonstrated that autoreactive CD4+ recent thymic emigrants (RTEs) were retained and some were activated in the liver directly after their egress from the thymus. Educations from secondary lymphoid organs were not required for this hepatic retention but TCR-MHC interaction in the liver was important for the activation of CD4+ liver RTEs. Compared to RTEs in the lymph nodes, liver RTEs exhibited higher TCR reactivity. CD4+ liver RTEs preferentially repopulated the liver and peyer’s patches when adoptively transferred into lymphoreplete mice. When transferred into RAG1-/- mice, liver but not lymph node RTEs caused T cell infiltration and severe inflammation in the lung. These data suggest that the liver may be the first checkpoint in the periphery to filter and retain autoreactive CD4+ thymic emigrants that escape from negative selection. Once unchecked in the absence of regulatory T cells in lymphopenic hosts, these cells could induce Th1 type autoimmunity primarily in the lung.