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Publication : Modulation of HLA-DQ-restricted collagen-induced arthritis by HLA-DRB1 polymorphism.

First Author  Taneja V Year  1998
Journal  Int Immunol Volume  10
Issue  10 Pages  1449-57
PubMed ID  9796911 Mgi Jnum  J:133940
Mgi Id  MGI:3784670 Citation  Taneja V, et al. (1998) Modulation of HLA-DQ-restricted collagen-induced arthritis by HLA-DRB1 polymorphism. Int Immunol 10(10):1449-57
abstractText  Mouse class II-deficient HLA-DQB1*0302, DQA1*0301 (DQ8) transgenic mice are susceptible to severe collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis. To examine whether polymorphism at the DRB1 locus can modulate DQ-restricted arthritis, we generated double-transgenic (DR/DQ) mice. HLA-DRB1*1502 (DR2) and DRB1*0301 (DR3) were introduced separately into CIA susceptible DQ8.Abeta transgenic mice to generate DQ8/DR2.Abeta and DQ8/ DR3.AbetaO mice. The HLA-DR molecules in these mice were found to be functional on the basis of their positive/negative selection of the Vbeta T cell repertoire. Introduction of the DR2 gene led to a significant decrease in disease incidence in DQ8.Abeta mice, while the DR3 transgene had no effect. In vitro T cell proliferative responses against bovine Cll collagen in primed mice were higher in DQ8/DR3 mice compared with DQ8/DR2 mice. Cytokine analysis showed a Th2 profile in DQ8/DR2 mice, while DQ8/DR3 mice showed a Th1 profile. These results suggest that DRB1 polymorphism can modulate the disease.
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