Depressed T-cell reactivity to recall antigens in rheumatoid arthritis

Abstract

Reactivity toward soluble recall antigens (Candida albicans, cytomegalovirus, herpes simplex, streptokinase-streptodornase, and influenza) was determined in cultures of peripheral blood mononuclear cells from 41 rheumatoid arthritis patients (with clinically active as well as inactive disease) and from 28 controls. In the group with clinically active rheumatoid arthritis we found an increased incidence of "anergy," defined as nonreactivity to three or more antigens. In an attempt to explain this decreased antigen reactivity, the latter was correlated with peripheral blood lymphocyte subsets, as defined by two-color immunofluorescence with a panel of eight monoclonal antibodies. We found a significantly lower number of memory T4 cells (CD4+CD45RA-) and a significantly higher number of the CD3-CD57+ (nonspecific suppressor) cells and of CD3-CD56+/CD16+ (natural killer) cells in anergic RA patients. In the total group of rheumatoid arthritis patients, the antigen reactivity correlated positively with the percentage of memory T4 cells. Antigen reactivity was negatively correlated with the percentage of CD3-CD57+ cells and of the CD3- natural killer cells in peripheral blood. Our data suggest that a decrease in memory T4 cells and an increase in nonspecific suppressor cells may contribute to the impaired cellular immune function in peripheral blood of rheumatoid arthritis patients.

Rheumatoid synovium is enriched in CD45RBdim mature memory T cells that are potent helpers for B cell differentiation

“…Rheumatoid synovial T cells are deficient in their ability to secrete IL-2 in response to activation by antigen or mitogens (13,33), and this defect in IL-2 production was confirmed in the present study. This observation was extended to investigate whether synovial T cells were globally or selectively deficient in their function.…”

“…Moreover, synovial T cells have been shown to produce substantially less interferon-y (IFNy) and IL-2 in vitro, and to proliferate less to mitogens or antigens than do T cells from either normal or RA peripheral blood (PB) (12). It has been argued therefore, that the role of T cells in synovial inflammation is limited (12,13). Indeed, macrophage-like and fibroblast-like synoviocytes also exhibit an activated phenotype in rheumatoid synovium, expressing high levels of class I1 MHC molecules.…”

CD4+CD28null T Cells in Autoimmune Disease: Pathogenic Features and Decreased Susceptibility to Immunoregulation

“…In general, it has been extremely difficult to demonstrate T cell reactivity against joint derived autoantigens such as hCII in RA patients. One cause may reside in the observed T cell hyporesponsiveness toward recall Ags in RA patients (37,38). Otherwise, a partial tolerization to hCII may account for the absence of a proliferative response toward hCII in RA patients.…”

Defective TCR-mediated signaling in synovial T cells in rheumatoid arthritis

“…This hyporesponsiveness is reflected by the absence or low levels of T cell-derived cytokines such as IFN-7 and IL-2 at the site of inflammation (9-12). Furthermore, RA T cells show depressed in vitro responses to recall Ags (13,14) and mitogenic stimulation (1 5-1 8), poor helper function (l9), and reduced autologous mixed lymphocyte responses (20,21).…”