Characterization of proteoglycan-reactive T cell lines and hybridomas from mice with proteoglycan-induced arthritis.
Hyperimmunization with chondroitin sulfate-depleted fetal human cartilage proteoglycan (HFPG) leads to the development of peripheral arthritis and spondylitis in BALB/c mice. Chondroitin-sulfate-depleted adult human cartilage proteoglycan (HAPG) is much less effective at inducing arthritis. These observations suggest age differences in the presence of arthritogenic proteoglycan (PG) epitopes. Earlier studies from this laboratory have indicated an important role for PG-reactive T cells in the pathogenesis of this arthritis model. To investigate further the cellular immunity to PG in mice, two T cell lines, JY.A and JY.D, and two T cell hybridomas, TH5 and TH14, were isolated from mice with PG-induced arthritis and characterized. Two patterns of reactivity to PG emerged from the analysis of these T cells. One pattern, as demonstrated by the T cell line JY.D and the two T cell hybridomas, TH5 and TH14, was characterized by reactivity to HFPG, HAPG, chondroitin sulfate-depleted bovine cartilage PG, the G1 domain (hyaluronate binding region) of bovine cartilage PG and bovine link protein. The epitope(s) recognized by these T cells appear to be part of the homologous regions shared between the G1 domain and the link protein. The second pattern of reactivity, as demonstrated by the T cell line JY.A, was characterized by reactivity to HFPG but not to HAPG or the other PG Ag or bovine link protein. All the T cell lines and hybridomas had a CD4+, CD8- phenotype, possibly belonged to the TH1 subset (IL-2+, IL-4-), and were MHC class II restricted. These studies indicate that HFPG has T cell epitopes in common with HAPG (such as in the G1 domain) and different than those in HAPG. The significance of this data in terms of PG structure, changes with age, and induction of arthritis remains to be established.
Shriners Hospital for Crippled Children, Department of Surgery, McGill University, Montreal, Quebec, Canada.
J Y
JY
Leroux
A R
AR
Poole
C
C
Webber
V
V
Vipparti
H U
HU
Choi
L C
LC
Rosenberg
S
S
Banerjee
D000818:Animals; D001168:Arthritis / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006825:Hybridomas / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D011509:Proteoglycans / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D011509:Proteoglycans