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Publication : The thymic niche does not limit development of the naturally diverse population of mouse regulatory T lymphocytes.

First Author  Romagnoli P Year  2012
Journal  J Immunol Volume  189
Issue  8 Pages  3831-7
PubMed ID  22988035 Mgi Jnum  J:190638
Mgi Id  MGI:5449325 Doi  10.4049/jimmunol.1201564
Citation  Romagnoli P, et al. (2012) The thymic niche does not limit development of the naturally diverse population of mouse regulatory T lymphocytes. J Immunol 189(8):3831-7
abstractText  Thymus-derived CD4(+)Foxp3(+) regulatory T lymphocytes (Tregs) play a central role in the suppression of immune responses to self-antigens and thus avoid autoimmune disorders. It remains unclear if the specialized thymic niche controls the number of differentiating Tregs. We investigated development of murine Tregs from precursors expressing the naturally very large repertoire of TCRs. By analyzing their developmental kinetics, we observed that differentiating Tregs dwell in the thymus approximately 1 d longer than their conventional T cell counterparts. By generating hematopoietic chimeras with very low proportions of trackable precursors, we could follow individual waves of developing T cells in the thymus. We observed strongly increased proportions of Tregs at the end of the waves, confirming that these cells are the last to leave the thymus. To assess whether the thymic niche limits Treg development, we generated hematopoietic chimeras in which very few T cell precursors could develop. The substantial increase in the proportion of Tregs we found in these mice suggested a limiting role of the thymic niche; however, this increase was accounted for entirely by the prolonged thymic dwell time of Tregs. We conclude that, when precursors express a naturally diverse TCR repertoire, the thymic niche does not limit differentiation of Tregs.
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