HIGH-LEVEL OF INTERLEUKIN-10 PRODUCTION BY THE ACTIVATED T-CELL POPULATION WITHIN THE RHEUMATOID SYNOVIAL-MEMBRANE

Objective, To characterize the cytokine profile of the activated T cell population derived from the synovial membrane of rheumatoid arthritis (RA) patients. Methods, Interleukin-% (IL-2) was used to select for in vivo-activated T cells from the synovial membrane of 2 patients with RA, and the cells were cloned nonspecifically. The cytokine production profile of these clones was compared with that of clones derived from peripheral blood monocytes (PBM) by stimulating all clones for 24 hours with immobilized anti-CD3 (coated at 10 mu g/ml) or phorbol-12-myristate-13-acetate (10 ng/ml) plus soluble anti-CD3 (1 mu g/ml). Interferon-gamma (IFN gamma), IL-4, and IL-10, the cytokines that discriminate between Th1 and Th2 cells and are involved in immunoregulation, were assayed by enzyme-linked immunosorbent assay. Results, There was a difference in the cytokines produced by the clones derived from the rheumatoid membranes compared with clones derived from the periphery, Clones derived from both membranes and PBM were mostly IFN gamma-producers, i.e., either a Th0 or a Th1 profile, There was a high proportion of IFN gamma/high IL-10-producing cells derived from the joint, but not from the periphery, Of clones derived from the synovial membrane of each of 2 RA patients, 100% and 50% produced both 1-10 ng/ml IFN gamma and >7 ng/ml IL-10, compared with <7% of clones derived from normal or RA peripheral blood, In addition, when autologous membrane and PBM were compared, the mean concentration of IL-10 produced by the clones derived from the synovial membrane sample was significantly different from those produced by clones derived from peripheral blood (P < 0.02). Conclusion, The cytokine profile of the T cell clones that were obtained from the RA joint after expansion with IL-2 is distinct from that of the T cells that are predominant in PBM, This supports the concept that the T cell subsets that accumulate in the joint are not a random sample, The high level of IL-10 production by clones derived from the synovium suggests that this cytokine may be a major contributor to the endogenous immunosuppression that occurs in RA.