Expression and function of inducible co-stimulator in patients with systemic lupus erythematosus: possible involvement in excessive interferon-gamma and anti-double-stranded DNA antibody production

Arthritis Res Ther. 2006;8(3):R62. doi: 10.1186/ar1928. Epub 2006 Mar 22.


Inducible co-stimulator (ICOS) is the third member of the CD28/cytotoxic T-lymphocyte associated antigen-4 family and is involved in the proliferation and activation of T cells. A detailed functional analysis of ICOS on peripheral blood T cells from patients with systemic lupus erythematosus (SLE) has not yet been reported. In the present study we developed a fully human anti-human ICOS mAb (JTA009) with high avidity and investigated the immunopathological roles of ICOS in SLE. JTA009 exhibited higher avidity for ICOS than a previously reported mAb, namely SA12. Using JTA009, ICOS was detected in a substantial proportion of unstimulated peripheral blood T cells from both normal control individuals and patients with SLE. In CD4+CD45RO+ T cells from peripheral blood, the percentage of ICOS+ cells and mean fluorescence intensity with JTA009 were significantly higher in active SLE than in inactive SLE or in normal control individuals. JTA009 co-stimulated peripheral blood T cells in the presence of suboptimal concentrations of anti-CD3 mAb. Median values of [3H]thymidine incorporation were higher in SLE T cells with ICOS co-stimulation than in normal T cells, and the difference between inactive SLE patients and normal control individuals achieved statistical significance. ICOS co-stimulation significantly increased the production of IFN-gamma, IL-4 and IL-10 in both SLE and normal T cells. IFN-gamma in the culture supernatants of both active and inactive SLE T cells with ICOS co-stimulation was significantly higher than in normal control T cells. Finally, SLE T cells with ICOS co-stimulation selectively and significantly enhanced the production of IgG anti-double-stranded DNA antibodies by autologous B cells. These findings suggest that ICOS is involved in abnormal T cell activation in SLE, and that blockade of the interaction between ICOS and its receptor may have therapeutic value in the treatment of this intractable disease.

MeSH terms

  • Antibodies, Monoclonal
  • Autoantibodies / blood*
  • B-Lymphocytes / immunology
  • Coculture Techniques
  • Cytokines / blood
  • DNA / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Interferon-gamma / blood*
  • Interleukin-10 / blood
  • Interleukin-2 / genetics
  • Interleukin-2 / physiology*
  • Interleukin-4 / blood
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology*
  • Lymphocyte Activation
  • Male
  • Reference Values
  • T-Lymphocytes / immunology


  • Antibodies, Monoclonal
  • Autoantibodies
  • Cytokines
  • Immunoglobulin G
  • Interleukin-2
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma
  • DNA