HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Related articles in The JI Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Latham, K. A. Articles by Rosloniec, E. F. Search for Related Content PubMed PubMed Citation Articles by Latham, K. A. Articles by Rosloniec, E. F.

Ex Vivo Characterization of the Autoimmune T Cell Response in the HLA-DR1 Mouse Model of Collagen-Induced Arthritis Reveals Long-Term Activation of Type II Collagen-Specific Cells and Their Presence in Arthritic Joints¹

Kary A. Latham, Karen B. Whittington^*, Ruohong Zhou, Zhaohui Qian and Edward F. Rosloniec^2,*,,

^* Veterans Affairs Medical Center, Memphis, TN 38104; and Departments of Medicine and Pathology, University of Tennessee Health Science Center, Memphis, TN 38163

Although the pathogenesis of collagen-induced arthritis (CIA), a model of rheumatoid arthritis, is mediated by both collagen-specific CD4⁺ T cells and Ab specific for type II collagen (CII), the role of CII-specific T cells in the pathogenesis of CIA remains unclear. Using tetrameric HLA-DR1 with a covalently bound immunodominant CII peptide, CII_259–273, we studied the development of the CII-specific T cell response in the periphery and arthritic joints of DR1 transgenic mice. Although the maximum number of DR1-CII-tetramer⁺ cells was detected in draining lymph nodes 10 days postimmunization, these T cells accounted for only 1% or less of the CD4⁺ population. After day 10, their numbers gradually decreased, but were still detectable on day 130. Examination of TCR expression and changes in CD62L, CD44^high, and CD69 expression by these T cells indicated that they expressed a limited TCR-BV repertoire and had clearly undergone activation. RT-PCR analysis of cytokine expression by the tetramer⁺ T cells compared with tetramer^– cells indicated the tetramer⁺ cells expressed high levels of Th1 and proinflammatory cytokines, including IL-2, IFN-, IL-6, TNF-, and especially IL-17. Additionally, analysis of the synovium from arthritic paws indicated that the same CD4⁺/BV8⁺/BV14⁺/tetramer⁺ T cells were present in the arthritic joints. These data demonstrate that although only small numbers of CII-specific T cells are generated during the development of CIA, these cells express very high levels of cytokine mRNA and appear to preferentially migrate to the arthritic joint, indicating a potential direct role of CII-specific T cells in the pathogenesis of CIA.

Related articles in The JI:

IN THIS ISSUE

The JI 2005 174: 3837-3838. [Full Text]  

This article has been cited by other articles:

				A. Linden A Role for the Cytoplasmic Adaptor Protein Act1 in Mediating IL-17 Signaling Sci. Signal., August 7, 2007; 2007(398): re4 - re4. [Abstract] [Full Text] [PDF]

				K. A. Richards, F. A. Chaves, F. R. Krafcik, D. J. Topham, C. A. Lazarski, and A. J. Sant Direct Ex Vivo Analyses of HLA-DR1 Transgenic Mice Reveal an Exceptionally Broad Pattern of Immunodominance in the Primary HLA-DR1-Restricted CD4 T-Cell Response to Influenza Virus Hemagglutinin J. Virol., July 15, 2007; 81(14): 7608 - 7619. [Abstract] [Full Text] [PDF]

				E. F. Rosloniec, R. A. Ivey III, K. B. Whittington, A. H. Kang, and H.-W. Park Crystallographic Structure of a Rheumatoid Arthritis MHC Susceptibility Allele, HLA-DR1 (DRB1*0101), Complexed with the Immunodominant Determinant of Human Type II Collagen J. Immunol., September 15, 2006; 177(6): 3884 - 3892. [Abstract] [Full Text] [PDF]