Down-regulation of the T cell receptor CD3 zeta chain in rheumatoid arthritis (RA) and its influence on T cell responsiveness

Clin Exp Immunol. 2000 Apr;120(1):174-82. doi: 10.1046/j.1365-2249.2000.01180.x.


T cells implicated in chronic inflammatory diseases such as RA respond weakly when stimulated in vitro with mitogen or antigen. The mechanism behind this hyporesponsiveness is unclear, but a depressed expression of the T cell receptor (TCR)-associated CD3zeta chain has been suggested. In the present work we describe a low expression of CD3zeta in synovial fluid (SF) T cells from RA patients compared with peripheral blood (PB) T cells, but no difference in CD3zeta expression between RA and healthy control PB T cells. In vitro studies demonstrated that granulocytes but not SF macrophages are able to down-regulate the expression of CD3zeta. Through stimulation with anti-CD3 antibodies we demonstrated that the TCR-dependent proliferative response was decreased in SF T cells compared with PB T cells. Stimulation with phorbol ester and ionomycin also resulted in a low proliferative response of SF T cells, indicating that both signal transduction through the TCR (stimulation with anti-CD3) and events further downstream in the signalling pathways (stimulation with phorbol ester and ionomycin) are affected. A similar depression of T cell activity was observed when induction of IL-2 and IL-4 was measured. However, SF T cells were not defective in the induction of interferon-gamma (IFN-gamma) when stimulated with phorbol myristate acetate (PMA)/ionomycin, in contrast to the diminished IFN-gamma response observed after stimulation with anti-CD3. This indicates that the hyporesponsiveness of SF T cells can not be generalized to all T cell functions. The differential response to external stimuli is likely to be of importance for the capacity of SF T cells to influence inflammatory reactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism
  • CD3 Complex / biosynthesis*
  • CD3 Complex / physiology
  • Cell Division / immunology
  • Cytokines / analysis
  • Cytokines / metabolism
  • Down-Regulation / immunology*
  • Female
  • Granulocytes / immunology
  • Granulocytes / metabolism
  • Humans
  • Interferon-gamma / analysis
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation / immunology*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Receptor-CD3 Complex, Antigen, T-Cell / immunology*
  • Receptor-CD3 Complex, Antigen, T-Cell / metabolism*
  • Synovial Fluid / cytology
  • Synovial Fluid / immunology
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*


  • CD3 Complex
  • CD3 antigen, zeta chain
  • Cytokines
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Interferon-gamma