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Objective: In rheumatoid arthritis (RA), treatment with tumor necrosis factor alpha (TNFalpha) binding agents has proven to be highly effective. Downregulation of the proinflammatory cytokine cascade and a reduced migration of leukocytes into the joints have been proposed as modes of action of TNFalpha blockade. We investigated whether alterations in the number of circulating pro- and antiinflammatory T cell subsets contribute to the therapeutic effect of monoclonal antibodies (mAb) against TNFalpha in RA patients., Methods: Phenotypic analysis of peripheral blood T cell subsets was performed on blood from RA patients before and after treatment with an anti-TNFalpha mAb., Results: An accumulation of primed CD45RA- T cells of both the CD4+ and the CD8+ T cell population was seen shortly after treatment. Most notably, within the CD4+,CD45RA- T cell subset, the number of interferon-gamma-producing T cells was significantly increased after anti-TNFalpha mAb treatment, resulting in a significant rise in the Th1:Th2 ratio. In addition, an increase in the number of CD4+ T cells expressing the homing receptor CD49d in high density was observed after treatment, which correlated positively with the increase in the Th1:Th2 ratio. Conclusion. We show that the Th1:Th2 ratio in the peripheral blood is raised by anti-TNFalpha mAb treatment.

Objective: The balance between T cells able to produce interferon gamma (IFN-gamma) (type 1) and interleukin-4 (IL-4) (type 2) is considered to be important in the development of autoimmunity. In this study, we quantitated the percentage of both cell types in synovial fluid (SF) and peripheral blood (PB) of rheumatoid arthritis (RA) patients, non-rheumatoid arthritis patients and healthy controls., Methods: After short-term stimulation of synovial mononuclear cells with phorbol ester and ionomycin, cytokine-producing cells were quantitated using an intracellular staining technique and flow cytometric analysis., Results: Although no significant differences in CD8 + cells were found, significantly higher percentages of IFN-gamma-producing CD4 + (Th 1) and IL-4-producing CD4 + (Th2) cells were found in the peripheral blood of RA patients in comparison with healthy controls. However, the Th1/Th2 ratio was not different between the two groups. Comparative studies between PB and SF showed that in both RA and non-RA patients, percentages of Th1 cells were higher in SF than in PB, while Th2 cells were preferentially found in the PB, resulting in a higher Th1/Th2 ratio in the SF. The Th1/Th2 ratio in the SF correlated with disease activity as estimated by the erythrocyte sedimentation rate., Conclusion: These results are in agreement with the hypothesis that Th1 cells preferentially home to inflamed joints in both RA and non-RA patients, but show that this does not result in an altered Th1/Th2 ratio in the PB of RA patients.