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Altered T Cell Differentiation in Patients with Early Rheumatoid Arthritis

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Chronic inflammation in rheumatoid arthritis (RA) is likely to be driven by activated Th1 cells without sufficient Th2 cell differentiation to down-modulate inflammation [1,2]. To test whether, in RA, Th cells express an alteration in their ability to differentiate into effector cells, we investigated Th cell differentiation in patients with early untreated RA and in age-and sex-matched controls in vitro. All patients had active RA with symptoms of the disease for 6 weeks to 12 months. A cell culture system was used that permitted the differentiation of Th effectors from resting memory T cells by short-term priming [3]. No difference in the cytokine secretion profile of freshly isolated T cells was detected between patients and controls. However, marked differences were found in the response to priming. Th2 cells could be induced in all healthy individuals by priming with anti-CD28 in the absence of TCR ligation. By contrast, priming under those conditions resulted in Th2 differentiation in only 9/24 RA patients. The addition of exogenous IL-4 could overcome the apparent Th2 differentiation defect in seven patients but was without effect in the remaining eight patients. In all patients, a marked decrease in IL-2 producing cells and a significant increase in well-differentiated Th1 cells that produced IFN-γ but no IL-2 was evident after priming with anti-CD3 and anti-CD28 [4]. The data suggest that CD4+ memory T cells from patients with early untreated RA manifest an intrinsic abnormality in their ability to differentiate into specific cytokine producing effector cells, which might contribute to the characteristic Th1 dominated chronic (auto)immune inflammation in RA.


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Skapenko, A., Wendler, J., Lipsky, P.E. et al. Altered T Cell Differentiation in Patients with Early Rheumatoid Arthritis. Arthritis Res Ther 1 (Suppl 1), S08 (1999).

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