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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD28 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Humans
  • Immune Tolerance
  • Immunosuppression
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocyte Subsets / physiology*
  • T-Lymphocytes, Regulatory / physiology*
  • Thymus Gland / physiology*


  • CD28 Antigens
  • CD8 Antigens