HLA-DRB1*0402 (DW10) transgene protects collagen-induced arthritis-susceptible H2Aq and DRB1*0401 (DW4) transgenic mice from arthritis.

Abstract

To investigate the role of HLA-DR4 in predisposition to arthritis, we generated transgenic mice carrying DRB1*0401 and DRB1*0402 genes. We have previously shown that DRB1*0401 molecule renders B10.RQB3 (H2A(q)) mice susceptible to porcine and human type II collagen-induced arthritis. We report that the introduction of DRB1*0402 transgene does not lead to development of arthritis in mice when they are immunized with porcine and human type II collagen. In addition, DRB1*0402 protects B10.RQB3 mice against developing arthritis with bovine type II collagen. These data show that DRB1 can modulate the disease mediated by A(q). In vivo depletion of DRB1*0402 did not lead to induction of collagen-induced arthritis in transgenic mice. In vitro cytokine analysis shows that mice protected from collagen-induced arthritis produce lower amounts of Th1 and higher levels of Th2 type cytokines upon immunization with type II collagen. Protection of mice was also related to higher apoptosis in DW10 mice as indicated by higher amounts of BclII in response to type II collagen. On the basis of our observations in HLA transgenic mice, we hypothesize that DRB1 polymorphism can modulate disease by shaping the T cell repertoire in thymus and select autoreactive T cells.

• Authors: Veena Taneja, Neelam Taneja, Marshall Behrens, Suchong Pan, Tad Trejo, Marie Griffiths, Harvinder Luthra, Chella S David
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 171 Issue 8 Pg. 4431-8 (Oct 15 2003) ISSN: 0022-1767 [Print] United States
• PMID: 14530370 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Autoantibodies
• Autoantigens
• Collagen Type II
• Epitopes
• H-2 Antigens
• H-2A antigen
• HLA-D Antigens
• HLA-DR Antigens
• HLA-DRB1 Chains
• HLA-DRB1*04:01 antigen
• HLA-DRB1*04:02 antigen
• HLA-Dw4 antigen
• Peptide Fragments
• Receptors, Antigen, T-Cell, alpha-beta

Topics

• Animals
• Antibody Specificity
• Apoptosis (genetics, immunology)
• Arthritis, Experimental (genetics, immunology, pathology, prevention & control)
• Autoantibodies (biosynthesis)
• Autoantigens (immunology)
• Cattle
• Collagen Type II (immunology)
• Epitopes (genetics, immunology)
• Gene Deletion
• Genetic Predisposition to Disease
• H-2 Antigens (genetics)
• HLA-D Antigens (biosynthesis, genetics, physiology)
• HLA-DR Antigens (biosynthesis, genetics, physiology)
• HLA-DRB1 Chains
• Humans
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Peptide Fragments (immunology)
• Receptors, Antigen, T-Cell, alpha-beta (biosynthesis, genetics)
• Self Tolerance (genetics)
• Swine
• Transgenes (physiology)