Altered lymphocyte reactivity in rheumatoid arthritis

Abstract

Blastogenic transformation of peripheral lymphocytes with phytohemagglutinin (PHA), conconavalin A (Con A), and pokeweed mitogen (PWM) was studied in 29 patients with rheumatoid arthritis (RA). The PHA response was depressed in a subgroup of RA patients with erosive disease. The Con A response was also depressed and paralleled the PHA response. The PWM response was not depressed. These results lend support to the hypothesis of a functional defect of cellular immunity in RA. It was shown that lymphocyte responsiveness to a single mitogen concentration is not an adequate assessment of the overall responsiveness of the lymphocytes tested.

Rheumatoid arthritis synovial T cells regulate transcription of several genes associated with antigen-induced anergy

“…Figure 5 illustrates pooled data for four patients and confirms that both Calmodulin and BF626661 are downregulated in SFMCs compared with PBMCs. This variation between transcript levels in RA SFMCs and PBMCs is consistent with the proliferative and signaling defects previously documented in these cell types (4,(23)(24)(25).…”

“…Additionally, RA T cells have an activated phenotype, characterized by upregulated expression of HLA-DR (3). On the other hand, these cells demonstrate features of anergy in vitro and do not proliferate when stimulated with mitogens or recall antigens (4). They are also unusually resistant to apoptosis (5).…”

Chronic exposure to tumor necrosis factor (TNF) in vitro impairs the activation of T cells through the T cell receptor/CD3 complex; reversal in vivo by anti-TNF antibodies in patients with rheumatoid arthritis.

“…Therefore, we decided to study cultures of antigen-specific T cell clones derived from normal individuals as a model system for investigating the long-term effects of TNF in vitro. Our data suggest that chronic exposure to bioactive TNF in vivo could account for some of the abnormal features of T cells derived from RA patients, such as impaired antigen and mitogen responses, and suppressed lymphokine production (33,34,35). Furthermore, studies of cell-mediated immune responses in RA patients before and after treatment with anti-TNF have confirmed our in vitro observations, demonstrating that TNF exerts suppressive effects on cellular responses in vivo.…”

Hyporesponsiveness of lymphocytes to virus antigens in rheumatoid arthritis

“…The decreased proliferative response of peripheral blood lymphocytes from RA patients to virus antigens which was demonstrated in the present study extends previous reports of diminished cellular immunity in RA (19)(20)(21)(22)(23)(24)28). Significantly fewer RA patients than controls responded to measles, rubella, and parainfluenza types 2 and 3 antigens, and the magnitude of response was significantly lower to rubella and parainfluenza types 1,2, and 3.…”