Auricular chondritis in NOD.DQ8.Aβo (Ag7–/–) transgenic mice resembles human relapsing polychondritis
Veena Taneja, … , Harvinder S. Luthra, Chella S. David
Veena Taneja, … , Harvinder S. Luthra, Chella S. David
Published December 15, 2003
Citation Information: J Clin Invest. 2003;112(12):1843-1850. https://doi.org/10.1172/JCI17450.
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Article Autoimmunity

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

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 (DQA1*0301, DQB1*0302) in a NOD background lacking endogenous class II molecules (Aβo). Upon immunization with type II collagen (CII), 85% of NOD.DQ8 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.

Authors

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

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(a) In vitro response of lymph node cells (LNCs) to chick CII (50 μg/ml)...
(a) In vitro response of lymph node cells (LNCs) to chick CII (50 μg/ml) from primed mice in transgenic and control mice. The results shown are mean ± SD of three experiments. SDs were lower than 10% in all experiments. (b) Inhibition of response was measured from LNCs cultured as above in the presence of specific Ab’s, DQ (IVD12) or mCD4 (GK1.5). The results are shown as the percentage of inhibition of response by a specific Ab. (c) NOD.DQ8 mice primed with CIX and CXI mount a dose-dependent response to a specific collagen. Cross-reactive response to CIX was observed in CII-immunized mice. The data is mean ± SD of all experiments. SI, stimulation index.