Association of Graves' disease and prevalence of circulating IFN-gamma-producing CD28(-) T cells

J Clin Immunol. 2008 Sep;28(5):464-72. doi: 10.1007/s10875-008-9213-4. Epub 2008 Aug 14.


Background: Peripheral blood CD4(+) and CD8(+) T-cell subsets lacking surface CD28 have been suggested to predispose patients to immune-mediated disorders.

Materials and methods: To determine the role of CD28(-) T-cell subset in Graves' disease (GD), we characterized peripheral blood CD4(+)CD28(-) and CD8(+)CD28(-) T cell from early onset GD patients.

Results and discussion: GD patients had significantly higher percentages of CD4(+)CD28(-) and CD8(+)CD28(-) T cells than did healthy donors. Both CD28(-) T cells expressed mostly CD45RO, suggesting that they are activated and/or are memory T cells. GD patient-derived CD4(+)CD28(-) and CD8(+)CD28(-) T cells produced more intracellular IFN-gamma than their counterparts from healthy donors. Furthermore, CD4(+)CD28(-) and CD8(+)CD28(-) T cells from GD patients with Graves' ophthalmopathy (GO) secreted higher level of intracellular IFN-gamma than those CD28(-) T cells from GD patients without GO. Retrospective analysis showed that the increased levels of CD4(+)CD28(-) T cells and their IFN-gamma-producing subgroups were positively correlated to the serum anti-thyrotropin receptor (TSHR) autoantibodies (TRAb). Our observations suggest that increased IFN-gamma-producing CD28(-) T cells in GD patients may play an important role in the pathogenesis of GD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / blood
  • CD28 Antigens
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Separation
  • Female
  • Flow Cytometry
  • Graves Ophthalmopathy / blood
  • Graves Ophthalmopathy / genetics
  • Graves Ophthalmopathy / immunology*
  • Humans
  • Immunologic Memory / genetics
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism*
  • Interleukin-2 / metabolism
  • Interleukin-4 / metabolism
  • Leukocyte Common Antigens / biosynthesis
  • Leukocyte Common Antigens / genetics
  • Male
  • Middle Aged
  • Receptors, Thyrotropin / immunology
  • Retrospective Studies
  • Statistics as Topic
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism


  • Autoantibodies
  • CD28 Antigens
  • Interleukin-2
  • Receptors, Thyrotropin
  • Interleukin-4
  • Interferon-gamma
  • Leukocyte Common Antigens