CD8+CD28- regulatory T lymphocytes prevent experimental inflammatory bowel disease in mice

Gastroenterology. 2006 Dec;131(6):1775-85. doi: 10.1053/j.gastro.2006.09.008. Epub 2006 Sep 8.


Background & aims: Immune responses to innocuous intestinal antigens appear tightly controlled by regulatory T lymphocytes. While CD4+ T lymphocytes have recently attracted the most attention, CD8+ regulatory T-cell populations are also believed to play an important role in control of mucosal immunity. However, CD8+ regulatory T-cell function has mainly been studied in vitro and no direct in vivo evidence exists that they can control mucosal immune responses. We investigated the capacity of CD8+CD28- T cells to prevent experimental inflammatory bowel disease (IBD) in mice.

Methods: CD8+CD28- regulatory T cells were isolated from unmanipulated mice and tested for their capacity to inhibit T-cell activation in allogeneic mixed lymphocyte cultures in vitro and to prevent IBD induced by injection of CD4+CD45RB(high) cells into syngeneic immunodeficient RAG-2 mutant mice.

Results: CD8+CD28- T lymphocytes inhibited proliferation and interferon gamma production by CD4+ responder T cells in vitro. CD8+CD28- regulatory T cells freshly isolated from spleen or gut efficiently prevented IBD induced by transfer of colitogenic T cells into immunodeficient hosts. Regulatory CD8+CD28- T cells incapable of producing interleukin-10 did not prevent colitis. Moreover, IBD induced with colitogenic T cells incapable of responding to transforming growth factor beta could not be prevented with CD8+CD28- regulatory T cells. CD8+CD28+ T cells did not inhibit in vitro or in vivo immune responses.

Conclusions: Our findings show that naturally occurring CD8+CD28- regulatory T lymphocytes can prevent experimental IBD in mice and suggest that these cells may play an important role in control of mucosal immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD28 Antigens / metabolism*
  • CD8 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • Immunotherapy / methods
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / pathology
  • Inflammatory Bowel Diseases / prevention & control*
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Phenotype
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Transforming Growth Factor beta / metabolism


  • CD28 Antigens
  • CD8 Antigens
  • Transforming Growth Factor beta
  • Interleukin-10
  • Interferon-gamma