T-cell functional defects in rheumatoid arthritis: Intrinsic or extrinsic?

Abstract

This study investigated two mechanisms which may underlie abnormal T-cell function [lymphocyte proliferation and interleukin-2 (IL-2) production] in rheumatoid arthritis (RA). These were: (a) a possible lack of the IL-2-producing CD4 +2H4 + lymphocytes and (b) the possible inhibitory role of monocytes and neutrophils. Numbers of CD4 +2H4 + cells did not differ between normal controls and patients with RA, although IL-2 produced by the peripheral blood mononuclear cells (PBMC) of the same individuals was markedly reduced in the patient group ( P < 0.001). Many rheumatoid peripheral blood mononuclear cell preparations, but very few control, were contaminated with neutrophils ( P < 0.001). This was more marked in patients with active RA than in those with inactive disease ( P < 0.001). Numbers of monocytes were similar in all groups. Monocyte depletion, or addition of indomethacin and/or catalase in PBMC, caused a significantly greater increase of responses in RA patients than in controls. This effect was significantly higher in patients with active disease than in the inactive group. These findings suggest that activated monocytes and neutrophils found in the rheumatoid PBMC preparations exert inhibitory effects mediated, in part, by the production of prostaglandins and reactive oxygen intermediates. Monocyte depletion and partial reconstitution resulted in significant increase of lymphocyte proliferation and IL-2 production in both controls and patients. None of the manipulations performed succeeded in normalizing the deficient rheumatoid T-cell responses. These data support the hypothesis that non-lymphoid cell populations play an important role in the T-cell dysfunction characteristic of RA. This may explain the differences in the functional capacity of lymphocytes observed between cells derived from different sites or different stages of the disease.