Article

Down‐regulation of the T cell receptor CD3ζ chain in rheumatoid arthritis (RA) and its influence on T cell responsiveness

Department of Biomedicine, Division of NBC-Defence, Defence Research Establishment, Umeå, and; Department of Clinical Immunology, University Hospital, Uppsala, Sweden
Clinical & Experimental Immunology (impact factor: 3.36). 03/2000; 120(1):174 - 182. DOI:10.1046/j.1365-2249.2000.01180.x pp.174 - 182

ABSTRACT 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 CD3ζ chain has been suggested. In the present work we describe a low expression of CD3ζ in synovial fluid (SF) T cells from RA patients compared with peripheral blood (PB) T cells, but no difference in CD3ζ 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 CD3ζ. 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-γ) when stimulated with phorbol myristate acetate (PMA)/ionomycin, in contrast to the diminished IFN-γ 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.

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Keywords

anti-CD3 antibodies
 
CD3ζ expression
 
depressed expression
 
diminished IFN-γ response
 
healthy control PB T cells
 
influence inflammatory reactions
 
low expression
 
low proliferative response
 
PB T cells
 
phorbol ester
 
phorbol myristate acetate
 
SF macrophages
 
SF T cells
 
similar depression
 
T cell functions
 
T cell receptor
 
T cells
 
TCR)-associated CD3ζ chain
 
TCR-dependent proliferative response
 
vitro studies