Perforin deficiency attenuates collagen-induced arthritis

K Bauer, A Knipper, H Tu-Rapp, D Koczan, HJ Kreutzer, H Nizze, E Mix, HJ Thiesen, Rikard Holmdahl, SM Ibrahim

Research output: Contribution to journalArticlepeer-review

12 Citations (SciVal)

Abstract

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.
Original languageEnglish
Pages (from-to)R877-R884
JournalArthritis Research and Therapy
Volume7
Issue number4
DOIs
Publication statusPublished - 2005

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Medical Inflammation Research (013212019)

Subject classification (UKÄ)

  • Rheumatology and Autoimmunity

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