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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

1
Institut National de la Santé et de la Recherche Médicale (Inserm) U1043, Toulouse, France.
2
Centre National de la Recherche Scientifique (CNRS) U5282, Toulouse, France.
3
Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, Toulouse, France.
4
Department of Pediatric Cardiology and Cardiovascular surgery, Children Hospital, University Hospital of Toulouse, Toulouse, France.

Abstract

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.

KEYWORDS:

regulatory T lymphocytes; thymus; tolerance

PMID:
26924728
PMCID:
PMC4863570
DOI:
10.1111/imm.12600
[Indexed for MEDLINE]
Free PMC Article

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