It has long been believed that all thymocytes are short-lived and that the thymocyte population is maintained by the continuous input of bone marrow-derived progenitor cells. Now, two studies published in the Journal of Experimental Medicine show that neonatal thymi contain thymocytes with a self-renewing capacity that can maintain the thymocyte population in the absence of any input from the bone marrow.
Martins et al. transplanted thymus lobes from newborn wild-type mice into mice deficient for RAG2, KIT and the common cytokine receptor γ-chain (which is required for interleukin-7 (IL-7) signalling). These mutant mice lack competitive haematopoietic stem cells and thus endogenous T cell development. They found that the number of double-positive (CD4+CD8+) thymocytes in these transplanted mice was similar to that in wild-type mice and that CD4+ and CD8+ T cells were released from the thymic graft. Furthermore, the T cell receptors (TCRs) underwent clonal rearrangement, and the authors also observed TCR clonal dominance, which may suggest that the thymocytes in these transplanted mice arose from the division of a limited number of cells. Finally, the authors showed that IL-7 receptor (IL-7R) signalling has a key role in the competition between thymus-resident and bone marrow-derived progenitors.
Peaudecerf et al. also reported thymus-autonomous T cell development in IL-7R-deficient mice transplanted with neonatal thymi. They identified a population of thymus-resident progenitors that expressed all the molecular markers of T cell progenitors and showed that the progenitors reconstitute a diverse peripheral T cell repertoire. These T cells were functional, as they cleared Listeria monocytogenes infection with similar kinetics to the T cells in normal mice, and they could function across histocompatibility barriers. Furthermore, T cells from allogeneic transplanted thymi did not induce graft-versus-host disease, suggesting that the neonatal T cells can become tolerant to host MHC molecules.
ORIGINAL RESEARCH PAPERS
Martins, V. C. et al. Thymus-autonomous T cell development in the absence of progenitor import. J. Exp. Med. 9 Jul 2012 (doi:10.1084/jem.20120846)
Peaudecerf, L. et al. Thymocytes may persist and differentiate without any input from bone marrow progenitors. J. Exp. Med. 9 Jul 2012 (doi:10.1084/jem.20120845)
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Leavy, O. Self-renewing thymocytes. Nat Rev Immunol 12, 550 (2012). https://doi.org/10.1038/nri3276
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DOI: https://doi.org/10.1038/nri3276