CD4+ recent thymic emigrants are biased to the TH2 effector lineage (82.15)

Abstract

Abstract Following intra-thymic development, T cells exit the thymus and join the peripheral T cell pool. These newly generated cells, termed recent thymic emigrants (RTEs), undergo phenotypic and functional maturation for the first 3 weeks they reside in the periphery. Using mice transgenic (Tg) for green fluorescent protein (GFP) driven by the Rag2 promoter (RAG2p-GFP Tg), in which GFP reliably distinguishes RTEs from their more mature naïve (MN) counterparts, our lab is able to isolate untouched RTEs for functional and phenotypic analysis. CD4+ RTEs exhibit defects in proliferation, IL-2Rα upregulation, and IL-2 production when stimulated through the TCR. We now show that CD4+ RTEs also exhibit defects in Th0, Th1, Th17 and Treg lineage commitment, with diminished cytokine production and transcription factor expression. In contrast to these diminished functions, RTEs are enriched for IL-4 producers when differentiated under Th2, but not Th0, conditions. This bias to the Th2 lineage may be due to regulated expression of T-bet, a key Th1 transcription factor. These data show that CD4+ RTEs represent a unique subset of the peripheral T cell pool, defined by a distinct interpretation of and response to immunological cues. These characteristics may be beneficial during the post-thymic maturation period to avoid inappropriate immune responses. This work was supported by R01AI064318 from the NIAID (with a supplement to DWH).