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.

TY - JOUR

T1 - 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.

AU - Bäcklund, Johan

AU - Treschow, Alexandra

AU - Firan, Mihail

AU - Malmström, Vivianne

AU - Issazadeh-Navikas, Shohreh

AU - Ward, E Sally

AU - Holmdahl, Rikard

N1 - Keywords: Age Factors; Animals; Arthritis; Collagen Type II; Epitopes, T-Lymphocyte; Glycosylation; Graft Rejection; Immune Tolerance; Immunodominant Epitopes; Lymphocytes; Male; Mice; Mice, Inbred C3H; Mice, Transgenic; Skin Transplantation

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

U2 - 10.1002/1521-4141(200206)32:6<1773::AID-IMMU1773>3.0.CO;2-Z

DO - 10.1002/1521-4141(200206)32:6<1773::AID-IMMU1773>3.0.CO;2-Z

M3 - Journal article

C2 - 12115661

SN - 0014-2980

VL - 32

SP - 1773

EP - 1783

JO - European Journal of Immunology

JF - European Journal of Immunology

IS - 6

ER -