Metabolic maturation, migration, and liver retention of CD4 single positive thymocytes and recent thymic emigrants (HEM4P.238)

Abstract

Abstract CD4 or CD8 single positive (SP) thymocytes, recent thymic emigrants (RTEs), and peripheral naïve T cells represent three consecutive cell populations along T cell maturation program. Except for negative selection in SP thymocytes, the importance and the regulation of this maturation is not well understood. In particular, little is known about the transition from mature SP to RTE and key events of this transition during and after thymic egress. We identified the phenotype of CD4+ pre-RTEs, a population of SPs that has acquired the thymic egress capability. A pro-oxidant shift and an increase of mitochondria content was found in pre-RTEs when compared to SPs with less functional maturity. The elevation of intracellular ROS was involved in promoting the functional maturation of these young T cells. After egress, autoreactive CD4+ pre-RTEs were retained and some were activated in the liver. Education from secondary lymphoid organs were not required for hepatic retention but TCR-MHC interaction in the liver was important for the activation of CD4+ liver RTEs. When transferred into RAG-/- mice, liver but not lymph node RTEs caused T cell infiltration and severe pulmonary inflammation, suggesting that the liver may be the first checkpoint in the periphery to filter and retain autoreactive CD4+ RTEs that escape from negative selection. Together, our results emphasize the complexity of SP-RTE maturation and the impact of various lymphoid tissue microenvironments on this maturation.