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Continued maturation of thymic emigrants in the periphery

Abstract

Developing thymocytes are selected for recognition of molecules encoded by the major histocompatibility complex, purged of self-reactive cells and committed to either the CD4 or CD8 lineage. The 1% of thymocytes that complete these tasks emigrate and join the population of peripheral lymphocytes. Whether T cell maturation is complete at the time of thymic exit has been a subject of debate. Using mice transgenic for green fluorescent protein driven by the recombination activating gene 2 promoter to identify recent thymic emigrants, we now show that T cell differentiation continues post-thymically, with progressive maturation of both surface phenotype and immune function. In addition, the relative contribution of CD4 and CD8 recent thymic emigrants was modulated as they entered the peripheral T cell pool. Thus, T cell maturation and subset contribution are both finalized in the lymphoid periphery.

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Figure 1: GFPhi peripheral T cells from RAG2p-GFP transgenic mice are RTEs.
Figure 2: RTEs undergo phenotypic maturation in the lymphoid periphery.
Figure 3: CD4+ RTEs undergo functional maturation in the lymphoid periphery.
Figure 4: CD8+ RTEs undergo functional maturation in the lymphoid periphery.
Figure 5: CD8+ RTEs respond to antigen in vivo less effectively than do GFPCD8+ T cells.
Figure 6: GFP expression does not inhibit proliferation of CD4+ or CD8+ T cells.
Figure 7: The CD4:CD8 ratio adjusts as RTEs contribute to the pool of mature peripheral T cells.
Figure 8: Both increased proliferation of CD8+ RTEs and decreased survival of CD4+ RTEs may contribute to the lowering of the CD4:CD8 ratio of RTEs after incorporation into the pool of mature peripheral T cells.

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Acknowledgements

Supported by National Institutes of Health grants AG13078 and AI44130 and a pilot grant from the Nathan Shock Center for Excellence in the Basic Biology of Aging (P.J.F.), F32 CA84736 (T.E.B.) and T32 AI07411 (C.J.C.).

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Correspondence to Pamela J Fink.

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Boursalian, T., Golob, J., Soper, D. et al. Continued maturation of thymic emigrants in the periphery. Nat Immunol 5, 418–425 (2004). https://doi.org/10.1038/ni1049

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