Regulatory functions of CD8+CD28- T cells in an autoimmune disease model

J Clin Invest. 2003 Oct;112(7):1037-48. doi: 10.1172/JCI17935.


CD8+ T cell depletion renders CD28-deficient mice susceptible to experimental autoimmune encephalomyelitis (EAE). In addition, CD8-/-CD28-/- double-knockout mice are susceptible to EAE. These findings suggest a role for CD8+ T cells in the resistance of CD28-deficient mice to disease. Adoptive transfer of CD8+CD28- T cells into CD8-/- mice results in significant suppression of disease, while CD8+CD28+ T cells demonstrate no similar effect on the clinical course of EAE in the same recipients. In vitro, CD8+CD28- but not CD8+CD28+ T cells suppress IFN-gamma production of myelin oligodendrocyte glycoprotein-specific CD4+ T cells. This suppression requires cell-to-cell contact and is dependent on the presence of APCs. APCs cocultured with CD8+CD28- T cells become less efficient in inducing a T cell-dependent immune response. Such interaction prevents upregulation of costimulatory molecules by APCs, hence decreasing the delivery of these signals to CD4+ T cells. These are the first data establishing that regulatory CD8+CD28- T cells occur in normal mice and play a critical role in disease resistance in CD28-/- animals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation
  • Antigen-Presenting Cells / physiology
  • CD28 Antigens / physiology*
  • CD8-Positive T-Lymphocytes / physiology*
  • Encephalomyelitis, Autoimmune, Experimental / etiology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Female
  • Interferon-gamma / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Myelin Proteins
  • Myelin-Associated Glycoprotein / immunology
  • Myelin-Oligodendrocyte Glycoprotein
  • Transforming Growth Factor beta / physiology


  • CD28 Antigens
  • Mog protein, mouse
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Transforming Growth Factor beta
  • Interferon-gamma