Collagen-induced arthritis and TCRs in SWR and B10.Q mice expressing an E(α)/(k) transgene

M. M. Griffiths, G. H. Nabozny, J. Hanson, D. S. Harper, S. McCall, K. G. Moder, G. W. Cannon, H. S. Luthra, C. S. David

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Abstract

B10.E(α)/(k) transgenic mice were mated with H2-E- B10.Q and SWR mice. F1 and F1 x parental strain backcross progeny were tested for arthritis and autoimmune reactivity to mouse type II collagen (MII) after immunization with bovine, chick, deer, or human type II collagen. The results were correlated with the H-2 haplotype (b/q vs q/q) and the TCR Vβ profile of peripheral blood T cells in each mouse. Hybrid progeny expressed TCR profiles different from either parent because of the TCR Vβ genomic deletions of SWR mice (Vβa), the wild-type TCR allele of C57Bl/10 (B10) mice (Vβb), and the intrathymic negative selection processes resulting from cell surface expression of E(α)/(k)-A(β)/(q) or E(β)/b-E(α')/(k), together with the integrated retroviral genes Mtv-9 originating in B10 mice and Mtv-7 (Mls- 1a) from SWR mice. (B10.E(α)/(k) x SWR)F1 mice developed higher IgG anti- MII Ab titers, but much milder arthritis than (B10.E x B10.Q)F1 mice. Expression of E(α)/(k) did not change the level of IgG anti-MII Ab nor the degree of susceptibility to collagen-induced arthritis (CIA) in the H-2(q/q) and H-2(b/q) progeny of (B10.E(α)/(k) x B10.Q)F1 x B10.Q matings, indicating that the Mtv-9-reactive, TCR Vβ5+, and Vβ11+ T cells are not critical to CIA. Among bovine type II collagen-immunized (B10.E(α)/(k) x SWR)F1 x SWR backcross mice: 1) arthritis severity is associated with the presence of Vβb (p ≤ 0.01) and expression of E(α)/(k) (p ≤ 0.05), but not with the MHC haplotype (b/q vs q/q); 2) regression analysis showed a significant association (R = 0.99) between IgG anti-MII Ab titers and the level of Mtv-7-reactive Vβ6+ T cells that was detectable in the IgG1, but not the IgG2a subclass. The data prompt the speculation that Mtv-7-reactive Vβ6+ (or Vβ7+) T cells in (B10.E(α)/(k) x SWR)F1 x SWR mice express Th2-type properties, and thus contribute to the combination of mild arthritis but high anti-MII Ab titers that characterize mice of SWR heritage.

Original languageEnglish (US)
Pages (from-to)2758-2768
Number of pages11
JournalJournal of Immunology
Volume153
Issue number6
StatePublished - 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Griffiths, M. M., Nabozny, G. H., Hanson, J., Harper, D. S., McCall, S., Moder, K. G., Cannon, G. W., Luthra, H. S., & David, C. S. (1994). Collagen-induced arthritis and TCRs in SWR and B10.Q mice expressing an E(α)/(k) transgene. Journal of Immunology, 153(6), 2758-2768.