T-cell receptors and collagen induced arthritis in H-2r mice.
Mouse strains B10, B10.RIII, RIIIS/J and the F1 and backcross progeny arising from them were tested for susceptibility to porcine type II collagen-induced arthritis (PII-CIA). The clinically severe arthritis of rapid onset that is characteristic of PII-immunized B10.RIII mice developed predominantly in hybrid offspring that had inherited at least one copy of wild type T cell receptor (TCR) genes (V beta b genotype) from the B10 or B10.RIII parent. The results indicate that, in the development of PII-CIA, mice expressing the H-2r/r haplotype preferentially utilize TCR V beta genes that are normally encoded within the TCR V beta genomic deletion region of RIIIS mice (V beta c). After aggressive immunization with PII, the use of alternative TCR V beta genes, encoded outside of the RIIIS deletion region, produced a high IgG antibody response that was cross-reactive with mouse type II collagen (MII) and equivalent to that of B10.RIII mice, but only a very mild, late onset arthritis of 56% (27/48) incidence in RIIIS male mice and 28% (10/35) incidence in RIIIS female mice. In comparison, B10.RIII mice routinely developed early onset of PII-CIA of significantly higher incidence (100%; p < 0.005) and four-fold greater severity, even after milder immunization protocols. The data are compatible with the proposal that the clinically weak CIA response of RIIIs mice may be primarily antibody driven while the severe CIA of B10.RIII mice reflects the added inflammatory effects of collagen-reactive effector-T cells in the joint.(ABSTRACT TRUNCATED AT 250 WORDS)
Griffiths
M M
MM
Veteran's Affairs Medical Center, University of Utah School of Medicine, Salt Lake City 84132.
Cole
B C
BC
Ito
J
J
Harper
D S
DS
Anderson
G D
GD
Cannon
G W
GW
Luthra
H S
HS
David
C S
CS
D000818:Animals; D001168:Arthritis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D003094:Collagen / Q000276:immunology*; D005260:Female; D005838:Genotype; D006183:H-2 Antigens / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D012727:Sex Characteristics; D013601:T-Lymphocytes / Q000276:immunology
D006183:H-2 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003094:Collagen