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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

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
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

Collagen-induced arthritis (CIA) is induced in H-2q 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.

Autoimmunity, Disease model, animal, Transgenic mouse, Transplantation tolerance
0014-2980
1773-1783
Bäcklund, Johan
b492facc-0572-4381-b0c9-2ea8af8af26a
Treschow, Alexandra
9c2c6783-2432-42a2-8f61-deffa412c224
Firan, Mihail
4eb11e8f-7fb6-483b-99d2-3f918a4325c5
Malmström, Vivianne
2f29bb3d-6136-4da9-8196-b580953f4bed
Issazadeh-Navikas, Shohreh
58d9e5d5-a444-4794-bb1e-48d0109989e7
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Holmdahl, Rikard
b6f8d2b9-b3d3-42d0-b450-20458767a8b4
Bäcklund, Johan
b492facc-0572-4381-b0c9-2ea8af8af26a
Treschow, Alexandra
9c2c6783-2432-42a2-8f61-deffa412c224
Firan, Mihail
4eb11e8f-7fb6-483b-99d2-3f918a4325c5
Malmström, Vivianne
2f29bb3d-6136-4da9-8196-b580953f4bed
Issazadeh-Navikas, Shohreh
58d9e5d5-a444-4794-bb1e-48d0109989e7
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Holmdahl, Rikard
b6f8d2b9-b3d3-42d0-b450-20458767a8b4

Bäcklund, Johan, Treschow, Alexandra, Firan, Mihail, Malmström, Vivianne, Issazadeh-Navikas, Shohreh, Ward, E. Sally and Holmdahl, Rikard (2002) 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. European Journal of Immunology, 32 (6), 1773-1783. (doi:10.1002/1521-4141(200206)32:6<1773::AID-IMMU1773>3.0.CO;2-Z).

Record type: Article

Abstract

Collagen-induced arthritis (CIA) is induced in H-2q 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.

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More information

Accepted/In Press date: 2 April 2002
e-pub ahead of print date: 29 May 2002
Published date: June 2002
Keywords: Autoimmunity, Disease model, animal, Transgenic mouse, Transplantation tolerance

Identifiers

Local EPrints ID: 425140
URI: http://eprints.soton.ac.uk/id/eprint/425140
ISSN: 0014-2980
PURE UUID: 1912e993-564f-45c6-8fbf-abc08a69da3f
ORCID for E. Sally Ward: ORCID iD orcid.org/0000-0003-3232-7238

Catalogue record

Date deposited: 11 Oct 2018 16:30
Last modified: 07 Oct 2020 02:22

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Contributors

Author: Johan Bäcklund
Author: Alexandra Treschow
Author: Mihail Firan
Author: Vivianne Malmström
Author: Shohreh Issazadeh-Navikas
Author: E. Sally Ward ORCID iD
Author: Rikard Holmdahl

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