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Reversal of tolerance induced by transplantation of skin expressing the immunodominant T cell epitope of rat type II collagen entitles development of collagen-induced arthritis but not graft rejection.

Bäcklund, Johan LU ; Treschow, Alexandra LU ; Firan, Mihail ; Malmström, Vivianne ; Issazadeh, Shohreh LU ; Ward, E Sally and Holmdahl, Rikard LU (2002) In European Journal of Immunology 32(6). p.1773-1783
Abstract
Collagen-induced arthritis (CIA) is induced in H-2(q) mice after immunization with rat type II collagen (CII). The immunodominant T cell epitope on heterologous CII has been located to CII256-270. We have previously shown that TSC transgenic mice, which express the heterologous epitope in type I collagen (CI), e.g. in skin, are tolerized against rat CII and resistant to CIA. In this study we transplanted skin from TSC transgenic mice onto non-transgenic CIA-susceptible littermates to investigate whether introduction of this epitope to a naïve immune system would lead to T cell priming and graft rejection or instead to tolerance and arthritis protection. Interestingly, TSC grafts were accepted and not even immunization of recipient mice... (More)
Collagen-induced arthritis (CIA) is induced in H-2(q) mice after immunization with rat type II collagen (CII). The immunodominant T cell epitope on heterologous CII has been located to CII256-270. We have previously shown that TSC transgenic mice, which express the heterologous epitope in type I collagen (CI), e.g. in skin, are tolerized against rat CII and resistant to CIA. In this study we transplanted skin from TSC transgenic mice onto non-transgenic CIA-susceptible littermates to investigate whether introduction of this epitope to a naïve immune system would lead to T cell priming and graft rejection or instead to tolerance and arthritis protection. Interestingly, TSC grafts were accepted and not even immunization of recipient mice with CII in adjuvant induced graft rejection. Instead, TSC skin recipients displayed a reduced T and B cell response to CII and were also protected from arthritis. However, additional priming could break arthritis protection and was accompanied by an increased T cell response to the grafted epitope. Strikingly, despite the regained T cell response, development of arthritis was not accompanied by graft rejection, showing that these immune-mediated inflammatory responses involve different mechanisms. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Epitopes, T-Lymphocyte, Glycosylation, Graft Rejection, Immune Tolerance, Immunodominant Epitopes, Lymphocytes : immunology, Male, Mice, Inbred C3H, Transgenic, Skin Transplantation : immunology, Collagen Type II : immunology, Age Factors, Animal, Arthritis : etiology
in
European Journal of Immunology
volume
32
issue
6
pages
1773 - 1783
publisher
John Wiley & Sons Inc.
external identifiers
  • wos:000176269000029
  • scopus:0036086532
ISSN
1521-4141
DOI
10.1002/1521-4141(200206)32:6<1773::AID-IMMU1773>3.0.CO;2-Z
language
English
LU publication?
yes
id
e38494d6-02d3-4c3a-9386-169c04b10ad8 (old id 109277)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12115661&dopt=Abstract
date added to LUP
2016-04-01 11:45:25
date last changed
2022-01-26 17:45:35
@article{e38494d6-02d3-4c3a-9386-169c04b10ad8,
  abstract     = {{Collagen-induced arthritis (CIA) is induced in H-2(q) mice after immunization with rat type II collagen (CII). The immunodominant T cell epitope on heterologous CII has been located to CII256-270. We have previously shown that TSC transgenic mice, which express the heterologous epitope in type I collagen (CI), e.g. in skin, are tolerized against rat CII and resistant to CIA. In this study we transplanted skin from TSC transgenic mice onto non-transgenic CIA-susceptible littermates to investigate whether introduction of this epitope to a naïve immune system would lead to T cell priming and graft rejection or instead to tolerance and arthritis protection. Interestingly, TSC grafts were accepted and not even immunization of recipient mice with CII in adjuvant induced graft rejection. Instead, TSC skin recipients displayed a reduced T and B cell response to CII and were also protected from arthritis. However, additional priming could break arthritis protection and was accompanied by an increased T cell response to the grafted epitope. Strikingly, despite the regained T cell response, development of arthritis was not accompanied by graft rejection, showing that these immune-mediated inflammatory responses involve different mechanisms.}},
  author       = {{Bäcklund, Johan and Treschow, Alexandra and Firan, Mihail and Malmström, Vivianne and Issazadeh, Shohreh and Ward, E Sally and Holmdahl, Rikard}},
  issn         = {{1521-4141}},
  keywords     = {{Epitopes; T-Lymphocyte; Glycosylation; Graft Rejection; Immune Tolerance; Immunodominant Epitopes; Lymphocytes : immunology; Male; Mice; Inbred C3H; Transgenic; Skin Transplantation : immunology; Collagen Type II : immunology; Age Factors; Animal; Arthritis : etiology}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{1773--1783}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{European Journal of Immunology}},
  title        = {{Reversal of tolerance induced by transplantation of skin expressing the immunodominant T cell epitope of rat type II collagen entitles development of collagen-induced arthritis but not graft rejection.}},
  url          = {{http://dx.doi.org/10.1002/1521-4141(200206)32:6<1773::AID-IMMU1773>3.0.CO;2-Z}},
  doi          = {{10.1002/1521-4141(200206)32:6<1773::AID-IMMU1773>3.0.CO;2-Z}},
  volume       = {{32}},
  year         = {{2002}},
}