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.

Research output: Contribution to journalArticle

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.

Details

Authors
  • Johan Bäcklund
  • Alexandra Treschow
  • Mihail Firan
  • Vivianne Malmström
  • Shohreh Issazadeh
  • E Sally Ward
  • Rikard Holmdahl
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area

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
Original languageEnglish
Pages (from-to)1773-1783
JournalEuropean Journal of Immunology
Volume32
Issue number6
Publication statusPublished - 2002
Publication categoryResearch
Peer-reviewedYes