Treatment with monoclonal anti-tumor necrosis factor α antibody results in an accumulation of TH1 CD4+ T cells in the peripheral blood of patients with rheumatoid arthritis

Objective. In rheumatoid arthritis (RA), treatment with tumor necrosis factor α (TNFα) binding agents has proven to be highly effective. Down- regulation of the proinflammatory cytokine cascade and a reduced migration of leukocytes into the joints have been proposed as modes of action of TNFα 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 TNFα 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-TNFα 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-γ-producing T cells was significantly increased after anti-TNFα 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-TNFα mAb treatment.