CD4+ recent thymic emigrants are biased to the Th2 lineage (99.14)

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. Activated CD4+ RTEs exhibit defects in IL-2Rα upregulation, proliferation and IL-2 production. We now show that CD4+ RTEs are defective in T helper (Th) 0, Th1, Th17 and regulatory T cell lineage commitment, with dampened cytokine production and transcription factor expression. RTE Th lineage commitment is not globally impaired, however, as CD4+ RTES are biased toward the Th2 lineage, with IL-4, IL-5 and IL-13 production that is enhanced compared to that by identically treated mature T cells. This bias in RTEs likely results from dampened negative regulation of the Th2 lineage by diminished levels of T-bet, a key Th1 transcription factor. CD4+ RTEs are thus a transitional population defined by their distinct interpretation of, and response to, immunological cues. These characteristics may be beneficial during the post-thymic maturation period to avoid inappropriate immune responses, particularly in lymphopenic neonates and adults.