Auricular chondritis in NOD.DQ8.Abetao (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 (DQA10301, DQB10302) in a NOD background lacking endogenous class II molecules (Abetao). 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+CD44(hi)CD62L(lo), 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
Journal	The Journal of clinical investigation (J Clin Invest) Vol. 112 Issue 12 Pg. 1843-50 (Dec 2003) ISSN: 0021-9738 [Print] United States
PMID	14679179 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Antigens, CD Antigens, Differentiation CD4 Antigens CTLA-4 Antigen CTLA4 protein, human Ctla4 protein, mouse Cytokines HLA-DQ Antigens HLA-DQ1 antigen HLA-DQ8 antigen Hyaluronan Receptors Receptors, Interleukin-2 L-Selectin Collagen
Topics	Animals Antigens, CD Antigens, Differentiation (biosynthesis) CD4 Antigens (biosynthesis) CTLA-4 Antigen Cartilage (pathology) Cell Division Chickens Collagen (metabolism) Cytokines (metabolism) Disease Models, Animal Dose-Response Relationship, Drug Ear (pathology) Female Flow Cytometry HLA-DQ Antigens (metabolism) Humans Hyaluronan Receptors (biosynthesis) L-Selectin (biosynthesis) Male Mice Mice, Inbred NOD Mice, Transgenic Polychondritis, Relapsing (genetics) Receptors, Interleukin-2 (biosynthesis) T-Lymphocytes (cytology) Time Factors Transgenes

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