T cells that are naturally tolerant to cartilage-derived type II collagen are involved in the development of collagen-induced arthritis.
The immunodominant T-cell epitope that is involved in collagen-induced arthritis (CIA) is the glycosylated type II collagen (CII) peptide 256-270. In CII transgenic mice, which express the immunodominant CII 256-270 epitope in cartilage, the CII-specific T cells are characterized by a partially tolerant state with low proliferative activity in vitro, but with maintained effector functions, such as IFN-gamma secretion and ability to provide B cell help. These mice were still susceptible to CIA. The response was mainly directed to the glycosylated form of the CII 256-270 peptide, rather than to the nonglycosylated peptide. Tolerance induction was rapid; transferred T cells encountered CII within a few days. CII immunization several weeks after thymectomy of the mice did not change their susceptibility to arthritis or the induction of partial T-cell tolerance, excluding a role for recent thymic emigrants. Thus, partially tolerant CII autoreactive T cells are maintained and are crucial for the development of CIA.
Malmström
V
V
Section for Medical Inflammation Research, Lund University, Lund, Sweden.
Bäcklund
J
J
Jansson
L
L
Kihlberg
J
J
Holmdahl
R
R
D000818:Animals; D001168:Arthritis / Q000097:blood / Q000276:immunology*; D002356:Cartilage / Q000276:immunology*; D002478:Cells, Cultured; D003094:Collagen / Q000276:immunology*; D006031:Glycosylation; D007074:Immunoglobulin G / Q000097:blood; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D007074:Immunoglobulin G; D010455:Peptides; D003094:Collagen