Susceptibility to collagen-induced arthritis is modulated by TGFβ responsiveness of T cells

作者：Christoph Schramm, Jörg Kriegsmann, Martina Protschka, Samuel Huber, Torsten Hansen, Edgar Schmitt, Peter R. Galle, Manfred Blessing · 发表于：Arthritis Research & Therapy · 年份：2004 · DOI：10.1186/ar1039 · 被引用次数：42 · 研究领域：TGF-β signaling in diseases、Cell Adhesion Molecules Research、NF-κB Signaling Pathways

The objective of our study was to determine the regulatory effects that endogenous transforming growth factor beta (TGFbeta) exerts on T cells in the pathogenesis of collagen-induced arthritis (CIA). CIA was induced in transgenic mice expressing a dominant negative TGFbeta type II receptor in T cells under the control of the human CD2 promoter. Clinical and histological arthritis scores were determined and experiments on disease induction and the healing phase of disease were performed. The proliferation and cytokine production of draining lymph node cells in vitro were analyzed. Transgenic mice were more susceptible to induction of CIA. The overall incidence was higher in transgenic mice than in wild-type mice (57% vs 35%, P < 0.05). Affected transgenic animals displayed a significantly higher clinical (4.5 +/- 0.6 vs 1.67 +/- 0.19, P = 0.001) and histological arthritis score (8.01 +/- 0.9 vs 4.06 +/- 1.1, P < 0.05). Draining lymph node cells of transgenic mice secreted more tumor necrosis factor alpha and IFNgamma and proliferated more vigorously in response to collagen type II and upon CD3/CD28 costimulation in vitro. Therefore, the regulation of T cells by endogenous TGFbeta is important for the maintenance of joint integrity after arthritis induction. Defects in TGFbeta-signalling as a susceptibility factor for rheumatoid arthritis may warrant further investigation.