HLA-DQ8 transgenic mice are highly susceptible to collagen-induced arthritis: a novel model for human polyarthritis

doi:10.1084/jem.183.1.27

This Article

	Full Text (PDF, 3790K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Nabozny, G. H.
	Articles by David, C. S.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Nabozny, G. H.
	Articles by David, C. S.


Social Bookmarking

	What's this?

ARTICLES

HLA-DQ8 transgenic mice are highly susceptible to collagen-induced arthritis: a novel model for human polyarthritis

GH Nabozny, JM Baisch, S Cheng, D Cosgrove, MM Griffiths, HS Luthra and CS David
Department of Immunology, Mayo Medical School, Rochester, Minnesota 55905, USA.

Genetic studies have indicated that susceptibility to rheumatoid arthritis (RA) maps to the HLA-DR locus of the major histocompatibility complex. Strong linkage disequilibrium between certain HLA-DQ genes and HLA-DR genes associated with RA, however, suggests that HLA-DQ molecules may also play a role in RA susceptibility. To examine the role of HLA-DQ molecules in arthritis, we generated transgenic mice expressing the DQA1*0301 and DQB1*0302 genes from an RA predisposing haplotype (DQ8/DR4Dw4). The transgenes were introduced into mouse class II-deficient H-2Ab0 mice, and their susceptibility to experimental collagen-induced arthritis was evaluated. The HLA-DQ8+,H-2Ab0 mice displayed good expression of the DQ8 molecule, while no surface expression of endogenous murine class II molecules could be detected. The DQ8 molecule also induced the selection of CD4+ T cells expressing a normal repertoire of V beta T cell receptors. Immunization of HLA- DQ8+,H-2Ab0 mice with bovine type II collagen (CII) induced a strong antibody response that was cross-reactive to homologous mouse CII. Also, in vitro proliferative responses against bovine CII, which were blocked in the presence of an antibody specific for HLA-DQ and mouse CD4, were detected. Finally, a severe polyarthritis developed in a majority of HLA-DQ8+,H-2Ab0 mice, which was indistinguishable from the disease observed in arthritis susceptible B10.T(6R) (H-2Aq) controls. In contrast, HLA-DQ8-,H-2Ab0 fullsibs did not generate CII antibody and were completely resistant to arthritis. Therefore, these results strongly suggest that HLA-DQ8 molecules contribute to genetic susceptibility to arthritis and also establish a novel animal model for the study of human arthritis.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Geluk, A., Lin, M. Y., van Meijgaarden, K. E., Leyten, E. M. S., Franken, K. L. M. C., Ottenhoff, T. H. M., Klein, M. R. (2007). T-Cell Recognition of the HspX Protein of Mycobacterium tuberculosis Correlates with Latent M. tuberculosis Infection but Not with M. bovis BCG Vaccination. Infect. Immun. 75: 2914-2921 [Abstract] [Full Text]
Roy, C. J., Warfield, K. L., Welcher, B. C., Gonzales, R. F., Larsen, T., Hanson, J., David, C. S., Krakauer, T., Bavari, S. (2005). Human Leukocyte Antigen-DQ8 Transgenic Mice: a Model To Examine the Toxicity of Aerosolized Staphylococcal Enterotoxin B. Infect. Immun. 73: 2452-2460 [Abstract] [Full Text]
Taneja, V., Taneja, N., Behrens, M., Griffiths, M. M., Luthra, H. S., David, C. S. (2005). Requirement for CD28 May Not Be Absolute for Collagen-Induced Arthritis: Study with HLA-DQ8 Transgenic Mice. J. Immunol. 174: 1118-1125 [Abstract] [Full Text]
Pajot, A., Pancre, V., Fazilleau, N., Michel, M.-L., Angyalosi, G., Ojcius, D. M., Auriault, C., Lemonnier, F. A., Lone, Y.-C. (2004). Comparison of HLA-DR1-restricted T cell response induced in HLA-DR1 transgenic mice deficient for murine MHC class II and HLA-DR1 transgenic mice expressing endogenous murine MHC class II molecules. Int Immunol 16: 1275-1282 [Abstract] [Full Text]
Havari, E., Lennon-Dumenil, A. M., Klein, L., Neely, D., Taylor, J. A., McInerney, M. F., Wucherpfennig, K. W., Lipes, M. A. (2004). Expression of the B7.1 Costimulatory Molecule on Pancreatic {beta} Cells Abrogates the Requirement for CD4 T Cells in the Development of Type 1 Diabetes. J. Immunol. 173: 787-796 [Abstract] [Full Text]
Stohl, W., Xu, D., Kim, K. S., David, C. S., Allison, J. P. (2004). MHC class II-independent and -dependent T cell expansion and B cell hyperactivity in vivo in mice deficient in CD152 (CTLA-4). Int Immunol 16: 895-904 [Abstract] [Full Text]
Kelemen, K., Gottlieb, P. A., Putnam, A. L., Davidson, H. W., Wegmann, D. R., Hutton, J. C. (2004). HLA-DQ8-Associated T Cell Responses to the Diabetes Autoantigen Phogrin (IA-2{beta}) in Human Prediabetes. J. Immunol. 172: 3955-3962 [Abstract] [Full Text]
Taylor, J. A., Havari, E., McInerney, M. F., Bronson, R., Wucherpfennig, K. W., Lipes, M. A. (2004). A Spontaneous Model for Autoimmune Myocarditis Using the Human MHC Molecule HLA-DQ8. J. Immunol. 172: 2651-2658 [Abstract] [Full Text]
Latham, K. A., Zamora, A., Drought, H., Subramanian, S., Matejuk, A., Offner, H., Rosloniec, E. F. (2003). Estradiol Treatment Redirects the Isotype of the Autoantibody Response and Prevents the Development of Autoimmune Arthritis. J. Immunol. 171: 5820-5827 [Abstract] [Full Text]
Elliott, J. F., Liu, J., Yuan, Z.-N., Bautista-Lopez, N., Wallbank, S. L., Suzuki, K., Rayner, D., Nation, P., Robertson, M. A., Liu, G., Kavanagh, K. M. (2003). Autoimmune cardiomyopathy and heart block develop spontaneously in HLA-DQ8 transgenic IA{beta} knockout NOD mice. Proc. Natl. Acad. Sci. USA 100: 13447-13452 [Abstract] [Full Text]
Taneja, V., Taneja, N., Behrens, M., Pan, S., Trejo, T., Griffiths, M., Luthra, H., David, C. S. (2003). HLA-DRB1*0402 (DW10) Transgene Protects Collagen- Induced Arthritis-Susceptible H2Aq and DRB1*0401 (DW4) Transgenic Mice from Arthritis. J. Immunol. 171: 4431-4438 [Abstract] [Full Text]
Cope, A. P. (2003). Exploring the reciprocal relationship between immunity and inflammation in chronic inflammatory arthritis. Rheumatology (Oxford) 42: 716-731 [Abstract] [Full Text]
Black, K. E., Murray, J. A., David, C. S. (2002). HLA-DQ Determines the Response to Exogenous Wheat Proteins: A Model of Gluten Sensitivity in Transgenic Knockout Mice. J. Immunol. 169: 5595-5600 [Abstract] [Full Text]
Taneja, V., Taneja, N., Paisansinsup, T., Behrens, M., Griffiths, M., Luthra, H., David, C. S. (2002). CD4 and CD8 T Cells in Susceptibility/Protection to Collagen-Induced Arthritis in HLA-DQ8-Transgenic Mice: Implications for Rheumatoid Arthritis. J. Immunol. 168: 5867-5875 [Abstract] [Full Text]
Paisansinsup, T., Deshmukh, U. S., Chowdhary, V. R., Luthra, H. S., Fu, S. M., David, C. S. (2002). HLA Class II Influences the Immune Response and Antibody Diversification to Ro60/Sjogren's Syndrome-A: Heightened Antibody Responses and Epitope Spreading in Mice Expressing HLA-DR molecules. J. Immunol. 168: 5876-5884 [Abstract] [Full Text]
Chapoval, S. P., Iijima, K., Marietta, E. V., Smart, M. K., Chapoval, A. I., Andrews, A. G., David, C. S. (2002). Allergic Inflammatory Response to Short Ragweed Allergenic Extract in HLA-DQ Transgenic Mice Lacking CD4 Gene. J. Immunol. 168: 890-899 [Abstract] [Full Text]
Brand, D. D., Myers, L. K., Whittington, K. B., Latham, K. A., Stuart, J. M., Kang, A. H., Rosloniec, E. F. (2002). Detection of Early Changes in Autoimmune T Cell Phenotype and Function Following Intravenous Administration of Type II Collagen in a TCR-Transgenic Model. J. Immunol. 168: 490-498 [Abstract] [Full Text]
Papouchado, B. G., Chapoval, S. P., Marietta, E. V., Weiler, C. R., David, C. S. (2001). Cockroach Allergen-Induced Eosinophilic Airway Inflammation in HLA-DQ/Human CD4+ Transgenic Mice. J. Immunol. 167: 4627-4634 [Abstract] [Full Text]
Stohl, W., Xu, D., Zang, S., Kim, K. S., Li, L., Hanson, J. A., Stohlman, S. A., David, C. S., Jacob, C. O. (2001). In vivo staphylococcal superantigen-driven polyclonal Ig responses in mice: dependence upon CD4+ cells and human MHC class II. Int Immunol 13: 1291-1300 [Abstract] [Full Text]
Raju, R., Spack, E. G., David, C. S. (2001). Acetylcholine Receptor Peptide Recognition in HLA DR3-Transgenic Mice: In Vivo Responses Correlate with MHC-Peptide Binding. J. Immunol. 167: 1118-1124 [Abstract] [Full Text]
Moustakas, A. K., van de Wal, Y., Routsias, J., Kooy, Y. M. C., van Veelen, P., Drijfhout, J. W., Koning, F., Papadopoulos, G. K. (2000). Structure of celiac disease-associated HLA-DQ8 and non-associated HLA-DQ9 alleles in complex with two disease-specific epitopes. Int Immunol 12: 1157-1166 [Abstract] [Full Text]
Krco, C. J., Watanabe, S., Harders, J., Griffths, M. M., Luthra, H., David, C. S. (1999). Identification of T Cell Determinants on Human Type II Collagen Recognized by HLA-DQ8 and HLA-DQ6 Transgenic Mice. J. Immunol. 163: 1661-1665 [Abstract] [Full Text]
Hall, F. C., Cope, A. P., Patel, S. D., Sonderstrup, G. (1999). Isolating the molecular suspect: HLA transgenic mice in the study of human autoimmune disease. Rheumatology (Oxford) 38: 697-704 [Full Text]
Yuasa, T., Kubo, S., Yoshino, T., Ujike, A., Matsumura, K., Ono, M., Ravetch, J. V., Takai, T. (1999). Deletion of Fc{gamma} Receptor IIB Renders H-2b Mice Susceptible to Collagen-induced Arthritis. JEM 189: 187-194 [Abstract] [Full Text]
Bradley, D. S., Das, P., Griffiths, M. M., Luthra, H. S., David, C. S. (1998). HLA-DQ6/8 Double Transgenic Mice Develop Auricular Chondritis Following Type II Collagen Immunization: A Model for Human Relapsing Polychondritis. J. Immunol. 161: 5046-5053 [Abstract] [Full Text]
Fridkis-Hareli, M., Rosloniec, E. F., Fugger, L., Strominger, J. L. (1998). Synthetic amino acid copolymers that bind to HLA-DR proteins and inhibit type II collagen-reactive T cell clones. Proc. Natl. Acad. Sci. USA 95: 12528-12531 [Abstract] [Full Text]
Geluk, A., Taneja, V., van Meijgaarden, K. E., Zanelli, E., Abou-Zeid, C., Thole, J. E.�R., de Vries, R. R.�P., David, C. S., Ottenhoff, T. H.�M. (1998). Identification of HLA class II-restricted determinants of Mycobacterium tuberculosis-derived proteins by using HLA-transgenic, class II-deficient mice. Proc. Natl. Acad. Sci. USA 95: 10797-10802 [Abstract] [Full Text]
Chapoval, S. P., Neeno, T., Krco, C. J., Marietta, E. V., Harders, J., David, C. S. (1998). HLA-DQ6 and HLA-DQ8 Transgenic Mice Respond to Ragweed Allergens and Recognize a Distinct Set of Epitopes on Short and Giant Ragweed Group 5 Antigens. J. Immunol. 161: 2032-2037 [Abstract] [Full Text]
Andersson, E. C., Hansen, B. E., Jacobsen, H., Madsen, L. S., Andersen, C. B., Engberg, J., Rothbard, J. B., McDevitt, G. S., Malmstrom, V., Holmdahl, R., Svejgaard, A., Fugger, L. (1998). Definition of MHC and T cell receptor contacts in the HLA-DR4restricted immunodominant epitope in type II collagen and characterization of collagen-induced arthritis in HLA-DR4 and human CD4 transgenic mice. Proc. Natl. Acad. Sci. USA 95: 7574-7579 [Abstract] [Full Text]
Wolyniec, W. W., De Sanctis, G. T., Nabozny, G., Torcellini, C., Haynes, N., Joetham, A., Gelfand, E. W., Drazen, J. M., Noonan, T. C. (1998). Reduction of Antigen-induced Airway Hyperreactivity and Eosinophilia in ICAM-1-deficient Mice. Am. J. Respir. Cell Mol. Bio. 18: 777-785 [Abstract] [Full Text]
Raju, R., Zhan, W.-Z., Karachunski, P., Conti-Fine, B., Sieck, G. C., David, C. (1998). Polymorphism at the HLA-DQ Locus Determines Susceptibility to Experimental Autoimmune Myasthenia Gravis. J. Immunol. 160: 4169-4174 [Abstract] [Full Text]
Rosloniec, E. F., Brand, D. D., Myers, L. K., Whittington, K. B., Gumanovskaya, M., Zaller, D. M., Woods, A., Altmann, D. M., Stuart, J. M., Kang, A. H. (1997). An HLA-DR1 Transgene Confers Susceptibility to Collagen-induced Arthritis Elicited with Human Type II Collagen. JEM 185: 1113-1122 [Abstract] [Full Text]