T-Cell Receptors and Collagen Induced Arthritis in H-2 ^R Mice

Abstract

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)

IFN deficient C57BL/6 (H-2b) mice develop collagen induced arthritis with predominant usage of T cell receptor V 6 and V 8 in arthritic joints

“…1 Subsequent studies have demonstrated the importance of CD4 + T helper (Th) cells, in particular Th1 subset, in CIA initiation and disease perpetuation, and the involvement of restricted T cell subsets in infiltration of the arthritic joint. [2][3][4][5][6] Current dogma concerning the pathogenesis of CIA suggests that limited epitopes on collagen type II (CII) molecule are presented in association with H-2 q or H-2 r class II MHC molecules to "autoimmune" T cell subsets expressing predominantly Vβ6 and Vβ8.1 T cell receptors (TCRs), which are regulated through the expression of minor lymphocyte stimulating antigens. 7 8 Disease induction is also dependent upon the production of antibodies reactive with autologous collagen, 9 and the subsequent expression of disease may be modulated through cytokine expression, both by increase in the inflammatory response and the differentiation of Th1/Th2 reactivity.…”

Role of superantigens in experimental arthritis

“…The TCRVfl haplotype in the RIIIS/J (designated TCRV/3 c) involves an even higher number of deleted TCRV/3 genes; 70% of the genes are deleted including both TCRV/38 genes and the TCRV/36 gene [47]. However, analyses of the data from an F2 analysis between B10.RIII and RIIIS/J, presented by Griffiths and coworkers [46], give no significant support for a modulatory role of the TCRb locus on arthritis susceptibility. This is in accordance with analyses of susceptibility to chronic experimental allergic encephalomyelitis in the same cross [48].…”

“…It has been proposed that T cells expressing V/36, which are encoded outside of the deletion in the TCRV/3 a haplotype, are important for development of CIA in H-2q mice [40]. The resistance to CIA induction in SWR mice has been explained as being due to the fact that the V/36-expressing T cells might develop into a regulatory Th2 phenotype rather than into a disease promoting Thl [46].…”

Circulating Immune Complexes Augment Severity of Antibody-Mediated Myasthenia Gravis in Hypogammaglobulinemic RIIIS/J Mice

“…Nevertheless, increased anti-AChR IgG production of RIIIS/J mice might not be the reason for increased EAMG susceptibility because of the generally accepted concept about the lack of correlation between anti-AChR Ab levels and EAMG or MG severity and also high serum anti-AChR IgG levels observed in F 1 mice, which demonstrate less susceptibility. Previously, it has been postulated that RIIIS/J mice are giving a more Ab-dependent and less T cellmediated response to the Ags because of their V␤ deletion, and thus developing weaker CIA (22). However, in our model, the lymph node cells of RIIIS/J mice gave a more prominent (but not significantly) lymphocyte proliferation response to AChR or immunodominant peptide (␣146 -162) stimulation than other strains (stimulation index for AChR-stimulated RIIIS/J lymph node cells was 3.2 vs 2.7 for B10.RIII mice), and also the mitogen response of lymph node T cells of RIIIS/J mice to Con A stimulation was equal to those of B6 and B10.RIII mice (data not shown).…”