Open Access Open Badges Research article

Perforin deficiency attenuates collagen-induced arthritis

Kristin Bauer1, Annika Knipper1, Hoang Tu-Rapp1, Dirk Koczan1, Hans-Jürgen Kreutzer2, Horst Nizze2, Eilhard Mix3, Hans-Juergen Thiesen1, Rikard Holmdahl4 and Saleh M Ibrahim1*

Author Affiliations

1 Institute of Immunology, University of Rostock, Rostock, Germany

2 Institute of Pathology, University of Rostock, Rostock, Germany

3 Institute of Neurology, University of Rostock, Rostock, Germany

4 Section for Medical Inflammation Research, Lund University, Lund, Sweden

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Arthritis Research & Therapy 2005, 7:R877-R884  doi:10.1186/ar1758

Published: 20 May 2005


Collagen-induced arthritis (CIA), an approved animal model for rheumatoid arthritis, is thought to be a T cell-dependent disease. There is evidence that CD8+ T cells are a major subset controlling the pathogenesis of CIA. They probably contribute to certain features of disease, namely tissue destruction and synovial hyperplasia. In this study we examined the role of perforin (pfp), a key molecule of the cytotoxic death pathway that is expressed mainly in CD8+ T cells, for the pathogenesis of CIA. We generated DBA/1J mice suffering from mutations of the pfp molecule, DBA/1J-pfp-/-, and studied their susceptibility to arthritis. As a result, pfp-deficient mice showed a reduced incidence (DBA/1J-pfp+/+, 64%; DBA/1J-pfp-/-, 54%), a slightly delayed onset (onset of disease: DBA/1J-pfp+/+, 53 ± 3.6; DBA/1J-pfp-/-, 59 ± 4.9 (mean ± SEM), and milder form of the disease (maximum disease score: DBA/1J-pfp+/+, 7.3 ± 1.1; DBA/1J-pfp-/-, 3.4 ± 1.4 (mean ± SEM); P < 0.05). Concomitantly, peripheral T cell proliferation in response to the specific antigen bovine collagen II was increased in pfp-/- mice compared with pfp+/+ mice, arguing for an impaired killing of autoreactive T cells caused by pfp deficiency. Thus, pfp-mediated cytotoxicity is involved in the initiation of tissue damage in arthritis, but pfp-independent cytotoxic death pathways might also contribute to CIA.