Altered development of collagen induced arthritis in T cell receptor V beta congenic B10.RIII mice.
Analysis of the mouse T cell receptor (TCR) V beta genome has revealed the existence of two distinct genotypes which bear deletions of certain V beta genes. Mice bearing the V beta a genotype lack approximately 50% of the V beta genome while V beta c mice lack 70% of the known V beta genes. Studies of the experimental model collagen induced arthritis (CIA) have indirectly suggested that the presence of truncated V beta genotypes may influence susceptibility to this autoimmune disease. In order to confirm the influence of V beta a and V beta c genotypes on CIA, we derived mice congenic for the known V beta haplotypes in the CIA susceptible B10.RIII (H-2r) background. Flow cytometric analysis of splenic lymphocytes revealed normal T cell levels in both B10.RIII-V beta congenic lines. Expectedly, a generalized increase in the expression of some non-deleted V beta genes was detected. In addition, the mice were immunized with porcine type II collagen and monitored for CIA. B10.RIII-V beta a mice showed little difference in arthritis incidence or severity versus B10.RIII, but a significant delay in the onset of CIA was seen. In contrast, B10.RIII-V beta c mice showed a marked decrease in arthritis incidence versus B10.RIII and the severity of CIA in arthritic mice was also significantly lower (p < 0.01). Thus, in the B10.RIII strain, the presence of truncated TCR V beta genotypes alters the development of CIA. These findings may shed light on the influence of TCR genotypes in the induction and development of human rheumatoid arthritis.
Nabozny
G H
GH
Department of Immunology, Mayo Graduate School of Medicine, Rochester, MN 55905, USA.
Hanson
J
J
Griffiths
M M
MM
Luthra
H S
HS
David
C S
CS
D000818:Animals; D000906:Antibodies / Q000097:blood; D001168:Arthritis / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D003094:Collagen / Q000276:immunology*; D003433:Crosses, Genetic; D005260:Female; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000737:chemistry
D000906:Antibodies; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003094:Collagen