High level of interleukin‐10 production by the activated t cell population within the rheumatoid synovial membrane

Abstract

Objective. To characterize the cytokine profile of the activated T cell population derived from the synovial membrane of rheumatoid arthritis (RA) patients. Methods. Interleukin‐2 (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 μg/ml) or phorbol‐12‐myristate‐13‐acetate (10 ng/ml) plus soluble anti‐CD3 (1 μg/ml). Interferon‐γ (IFNγ), 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 IFNγ‐producers, i.e., either a Th0 or a Th1 profile. There was a high proportion of IFNγ/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 IFNγ 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.

Functional Analysis of −571 IL-10 Promoter Polymorphism Reveals a Repressor Element Controlled by Sp1

“…Our demonstration that this allele results in higher levels of IL-10 production, which could thereby act to suppress the antineoplastic immune response, supports the negative impact of this polymorphism in NHL. Serum levels and ex vivo studies of monocytes and B cells from patients with SLE and rheumatoid arthritis have shown increased levels of IL-10 production (57,58). Several genetic studies have confirmed that the Ϫ571 polymorphism is overexpressed in populations of patients with SLE (52,59).…”

Role of chemokines and cytokines in a reactivation model of arthritis in rats induced by injection with streptococcal cell walls

“…Unstimulated CD4 ϩ T cells from synovial fluid produce large quantities of IL-4 and IL-10 and deficient levels of interferon-␥ and IL-2 [30]. In addition, synovial tissue lymphocytes produce significant quantities of IL-10 [31]. The diverse nature of the immune response in rheumatoid arthritis may reflect the complex immunoregulatory networks that are evident in human disease.…”

IL-10-Deficient B10.Q Mice Develop More Severe Collagen-Induced Arthritis, but Are Protected from Arthritis Induced with Anti-Type II Collagen Antibodies

“…Further to this, IL-10 is also abundantly expressed in the rheumatoid synovium (5), and it has been demonstrated that T cell clones from RA synovium produce higher levels of IL-10 than T cell clones derived from peripheral blood (6).…”