Role of Mls-1 locus and clonal deletion of T cells in susceptibility to collagen-induced arthritis in mice

G. D. Anderson, S. Banerjee, H. S. Luthra, C. S. David

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Abstract

The role of T cell-mediated and humoral immunity to type II collagen has been well documented in collagen-induced arthritis (CIA). Previous work from our laboratory has indicated that genomic deletions of TCR V(β) genes may play a role in CIA resistance in mice. This indicated a selectivity of TCR usage by autoreactive T cells in CIA in mice. Certain strains of mice, although having a normal genomic V(β) TCR repertoire, can show clonal deletion of peripheral T cells that bear specific V(β) gene products in their TCR. These clonally deleted T cells are reactive with self-Ag such as minor lymphocyte stimulation (Mls) Ag. An Mls-congenic strain, BALB.D2.Mlsa, which differs only at the Mls-1a locus from BALB/c (Mls-1b), was used to examine the effect of clonal deletion of Mls-1a-reactive T cells in CIA. These two strains were crossed to three CIA-susceptible strains, B10.RIII (H-2(r), Mls-1b), DBA/1 (H-2(q), Mls-1a), and B10.Q (H-2(q), Mls-1b), and the crosses were injected with type II collagen. A significantly decreased incidence of arthritis was observed in the (BALB.D2.Mlsa x B10.Q)F1 hybrids, compared with (BALB/c x B10.Q)F1 hybrids, upon immunization with chick type II collagen. The BALB.D2.Mlsa cross mice also had significantly lower levels of anti-mouse collagen antibodies. Flow cytometric analysis confirmed the clonal deletion of Mls-1a-reactive V(β)8.1, V(β)6, V(β)7, and V(β)9 subsets in the (BALB.D2.Mlsa x B10.Q)F1 hybrids. The study of H-2(q/d) mice in (BALB.D2.Mlsa x B10.Q) x B10.Q backcrosses demonstrated a significant correlation between CIA resistance and Mls-1a locus. On the other hand, B10.RIII crosses showed only a modest decrease in CIA incidence in the presence of Mls-1a. As expected, all the DBA/1 crosses had an equal incidence of CIA, which was somewhat less than that seen in DBA/1 mice themselves. These studies point out that the Mls-1a locus could play a role in decreasing CIA incidence by clonal deletion of T cells bearing specific V(β) TCR, which may be involved in the pathogenesis of CIA. The influence of the clonal deletion of T cells on CIA, and hence the usage of specific V(β) TCR by autoreactive anti-type II collagen T cells, however, depends not only on the source of the type II collagen and the MHC class II molecules involved but also on other background genes in mice.

Original languageEnglish (US)
Pages (from-to)1189-1193
Number of pages5
JournalJournal of Immunology
Volume147
Issue number4
StatePublished - Jan 1 1991

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Anderson, G. D., Banerjee, S., Luthra, H. S., & David, C. S. (1991). Role of Mls-1 locus and clonal deletion of T cells in susceptibility to collagen-induced arthritis in mice. Journal of Immunology, 147(4), 1189-1193.