Auricular chondritis in NOD.DQ8.Aβo (Ag7-/-) transgenic mice resembles human relapsing polychondritis

Veena D Taneja, Marie Griffiths, Marshall Behrens, Harvinder S. Luthra, Chella S. David

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Abstract

Relapsing polychondritis is a multisystem autoimmune disease involving cartilage destruction but no known causative antigen. HLA-DQ8 has been associated with various autoimmune diseases in humans. To study the role of DQ8 in autoimmune diseases, we have generated transgenic mice expressing DQ8 (QA1*0301, DQB1*0302) in a NOD background lacking endogenous class II molecules (Aβo). Upon immunization with type II collagen (CII), 85% of NOD.DQ8 of mice develop severe experimental polychondritis, auricular chondritis, and polyarthritis, with clinical and histological similarities to relapsing polychondritis (RP) in humans. CII-immunized mice mount a T cell response and produce Ab's to type IX collagen (CIX) and self-CII. Transgene-negative littermates do not develop any serological and clinical manifestations following immunization. B10.DQ8 transgenic mice develop polyarthritis and Ab's to CII only. The susceptibility to auricular chondritis in NOD.DQ8 mice can be attributed to response to CIX. A higher number of activated cells, CD4+CD44hiCD62Llo, and lower regulatory cells CD4+CD152+CD25+ were observed in NOD.DQ8 mice compared with B10.DQ8 mice. The NOD.DQ8 mice provide a model of RP with a high disease incidence and multiple organ involvement to investigate putative autoantigen and regulatory cells involved in disease pathogenesis. An experimental model restricted by the human class II molecule will be valuable when studying the role of various collagens in immunologic and pathologic responses in human RP.

Original languageEnglish (US)
Pages (from-to)1843-1850
Number of pages8
JournalJournal of Clinical Investigation
Volume112
Issue number12
DOIs
StatePublished - Dec 2003

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Relapsing Polychondritis
Transgenic Mice
Autoimmune Diseases
Arthritis
Immunization
Collagen Type IX
Collagen Type II
Autoantigens
Transgenes
Cartilage
Theoretical Models
Collagen
Cell Count
T-Lymphocytes
Antigens
Incidence

ASJC Scopus subject areas

  • Medicine(all)

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Auricular chondritis in NOD.DQ8.Aβo (Ag7-/-) transgenic mice resembles human relapsing polychondritis. / Taneja, Veena D; Griffiths, Marie; Behrens, Marshall; Luthra, Harvinder S.; David, Chella S.

In: Journal of Clinical Investigation, Vol. 112, No. 12, 12.2003, p. 1843-1850.

Research output: Contribution to journalArticle

Taneja, Veena D ; Griffiths, Marie ; Behrens, Marshall ; Luthra, Harvinder S. ; David, Chella S. / Auricular chondritis in NOD.DQ8.Aβo (Ag7-/-) transgenic mice resembles human relapsing polychondritis. In: Journal of Clinical Investigation. 2003 ; Vol. 112, No. 12. pp. 1843-1850.
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