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Perforin deficiency attenuates collagen-induced arthritis

Bauer, K; Knipper, A; Tu-Rapp, H; Koczan, D; Kreutzer, HJ; Nizze, H; Mix, E; Thiesen, HJ; Holmdahl, Rikard LU and Ibrahim, SM (2005) In Arthritis Research and Therapy 7(4). p.877-884
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Arthritis Research and Therapy
volume
7
issue
4
pages
877 - 884
publisher
BioMed Central
external identifiers
  • wos:000231020100026
  • pmid:15987490
  • scopus:33645504438
ISSN
1478-6362
DOI
10.1186/ar1758
language
English
LU publication?
yes
id
dca6585d-9bc9-4c91-aff5-591017b4e2c9 (old id 229841)
date added to LUP
2007-08-22 08:23:05
date last changed
2017-02-12 03:27:16
@article{dca6585d-9bc9-4c91-aff5-591017b4e2c9,
  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 &lt; 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.},
  author       = {Bauer, K and Knipper, A and Tu-Rapp, H and Koczan, D and Kreutzer, HJ and Nizze, H and Mix, E and Thiesen, HJ and Holmdahl, Rikard and Ibrahim, SM},
  issn         = {1478-6362},
  language     = {eng},
  number       = {4},
  pages        = {877--884},
  publisher    = {BioMed Central},
  series       = {Arthritis Research and Therapy},
  title        = {Perforin deficiency attenuates collagen-induced arthritis},
  url          = {http://dx.doi.org/10.1186/ar1758},
  volume       = {7},
  year         = {2005},
}