Open Access Open Badges Research article

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

Christoph Schramm1*, Jörg Kriegsmann2, Martina Protschka3, Samuel Huber1, Torsten Hansen4, Edgar Schmitt5, Peter Robert Galle1 and Manfred Blessing26

Author Affiliations

1 I. Medizinische Klinik, Johannes Gutenberg-Universität Mainz, Mainz, Germany

2 Gemeinschaftspraxis für Pathologie, Trier, Germany

3 I. Medizinische Klinik, Abteilung Pathophysiologie, Johannes Gutenberg-Universität Mainz, Mainz, Germany

4 Institut für Pathologie, Johannes Gutenberg-Universität Mainz, Mainz, Germany

5 Institut für Immunologie, Mainz, Germany

6 Biotechnologisch-Biomedizinisches Zentrum, Leipzig, Germany

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Arthritis Res Ther 2004, 6:R114-R119  doi:10.1186/ar1039

Published: 8 January 2004


The objective of our study was to determine the regulatory effects that endogenous transforming growth factor β (TGFβ) exerts on T cells in the pathogenesis of collagen-induced arthritis (CIA). CIA was induced in transgenic mice expressing a dominant negative TGFβ 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 α and IFNγ 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 TGFβ is important for the maintenance of joint integrity after arthritis induction. Defects in TGFβ-signalling as a susceptibility factor for rheumatoid arthritis may warrant further investigation.

dominant negative TGFβ type II receptor; IFNγ; transgenic mice