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

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.

Visualization and phenotyping of proinflammatory antigen-specific T cells during collagen-induced arthritis in a mouse with a fixed collagen type II-specific transgenic T-cell receptor β-chain

“…Recombinant MHC class II tetramers/multimers presenting CII peptides have previously been used to identify CII-specific T cells ex vivo in A q -expressing [21,22], DR4-expressing [23], and DR1-expressing mice [24]. Successful identification of CII-specific T cells in A q -expressing mice, however, required that the CII peptide had been covalently linked to the recombinant MHC class II molecule.…”

Inflammation Parameters, Xanthine Oxidase and Anti-Xanthine Oxidase Antibodies in Synovial Fluid of Patients Suffering from Arthritis

“…In the Western world more than 50% of RA patients are older than 65 years at diagnosis (1). The main pathological changes that occur in RA are of an autoimmune nature, chronic synovitis, cartilage destruction and bone erosion (2,3). It is also the most common systemic autoimmune disease and is characterized by the presence of various autoantibodies in serum and synovial fluid (SF) (4,5).…”

Treatment with total alkaloids from Radix Linderae reduces inflammation and joint destruction in type II collagen-induced model for rheumatoid arthritis

“…; IgG, immunoglobulin G; DTH, delayed type hypersensitivity; H&E, hematoxylin and eosin; Con A, concanavalin A; MTT, 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide; DMSO, dimethyl sulfoxide * Corresponding author. been defined, such as abnormal immunity, chronic synovitis, inflammatory cell infiltration, pannus formation, destruction of cartilage and bone erosion (Remmers et al, 2002;Lu et al, 2002;Backlund et al, 2002). The development of RA involves a complex interplay of several types of cells, including B and T lymphocytes, macrophages, fibroblast-like synoviocytes, endothelial cells and dendritic cells (Panayi, 1997;Firestein, 2003).…”