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Immunology. 2016 Jun;148(2):187-96. doi: 10.1111/imm.12600. Epub 2016 Mar 23.

Mouse and human CD8(+) CD28(low) regulatory T lymphocytes differentiate in the thymus.

Vuddamalay Y1,2,3, Attia M1,2,3, Vicente R1,2,3, Pomié C1,2,3, Enault G1,2,3, Leobon B4, Joffre O1,2,3, Romagnoli P1,2,3, van Meerwijk JP1,2,3.

Author information

Institut National de la Santé et de la Recherche Médicale (Inserm) U1043, Toulouse, France.
Centre National de la Recherche Scientifique (CNRS) U5282, Toulouse, France.
Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, Toulouse, France.
Department of Pediatric Cardiology and Cardiovascular surgery, Children Hospital, University Hospital of Toulouse, Toulouse, France.


Regulatory T (Treg) lymphocytes play a central role in the control of immune responses and so maintain immune tolerance and homeostasis. In mice, expression of the CD8 co-receptor and low levels of the co-stimulatory molecule CD28 characterizes a Treg cell population that exerts potent suppressive function in vitro and efficiently controls experimental immunopathology in vivo. It has remained unclear if CD8(+) CD28(low) Treg cells develop in the thymus or represent a population of chronically activated conventional T cells differentiating into Treg cells in the periphery, as suggested by their CD28(low) phenotype. We demonstrate that functional CD8(+) CD28(low) Treg cells are present in the thymus and that these cells develop locally and are not recirculating from the periphery. Differentiation of CD8(+) CD28(low) Treg cells requires MHC class I expression on radioresistant but not on haematopoietic thymic stromal cells. In contrast to other Treg cells, CD8(+) CD28(low) Treg cells develop simultaneously with CD8(+) CD28(high) conventional T cells. We also identified a novel homologous naive CD8(+) CD28(low) T-cell population with immunosuppressive properties in human blood and thymus. Combined, our data demonstrate that CD8(+) CD28(low) cells can develop in the thymus of mice and suggest that the same is true in humans.


regulatory T lymphocytes; thymus; tolerance

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