Matrix metalloproteinases as targets for the immune system during experimental arthritis.

Abstract

Novel therapies for rheumatoid arthritis aiming at intervention in the inflammatory process by manipulation of autoreactive T and B lymphocytes receive major interest. However, the development of such therapies is largely hampered by the lack of knowledge of self-Ags recognized during the disease process. Recently, we predicted putative T cell self-epitopes based on a computer search profile. In the present study, the predicted self-epitopes were tested for T cell recognition in two experimental arthritis models, and their arthritogenic capacity was analyzed. Fourteen of n = 51 predicted self-epitopes were recognized during experimental arthritis of which six were able to actively induce arthritis. Interestingly, three of these six peptides were derived from matrix metalloproteinases (MMP), and only T cells responsive to MMP-derived epitopes were able to passively transfer arthritis to naive rats. Moreover, we demonstrate the presence of Abs to MMP-3 during the course of adjuvant arthritis. Together these data indicate that MMPs play a pivotal role as target for T and B cells during the development of inflammatory arthritis. This finding sheds new light on the pathophysiological role of MMPs during arthritis and opens novel possibilities for Ag-specific immunotherapy.

• Authors: Jolanda H M van Bilsen, Josée P A Wagenaar-Hilbers, Mayken C J T Grosfeld-Stulemeijer, Maarten J F van der Cammen, Mariska E A van Dijk, Willem van Eden, Marca H M Wauben
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 172 Issue 8 Pg. 5063-8 (Apr 15 2004) ISSN: 0022-1767 [Print] United States
• PMID: 15067089 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Autoantibodies
• Autoantigens
• Diamines
• Epitopes, T-Lymphocyte
• Histocompatibility Antigens Class II
• Peptide Fragments
• Quaternary Ammonium Compounds
• dimethyldioctadecylammonium
• Matrix Metalloproteinases
• Matrix Metalloproteinase 3
• avridine

Topics

• Adjuvants, Immunologic (administration & dosage)
• Adoptive Transfer
• Animals
• Arthritis, Experimental (enzymology, immunology, pathology)
• Autoantibodies (biosynthesis)
• Autoantigens (administration & dosage, immunology, metabolism)
• B-Lymphocyte Subsets (immunology, metabolism)
• CD4-Positive T-Lymphocytes (immunology, transplantation)
• Cartilage, Articular (enzymology, immunology)
• Diamines (administration & dosage)
• Epitopes, T-Lymphocyte (administration & dosage, immunology, metabolism)
• Histocompatibility Antigens Class II (metabolism)
• Humans
• Immune System (enzymology)
• Lymph Nodes (enzymology, immunology)
• Matrix Metalloproteinase 3 (administration & dosage, immunology)
• Matrix Metalloproteinases (administration & dosage, immunology, metabolism)
• Peptide Fragments (administration & dosage, immunology, metabolism)
• Protein Binding (immunology)
• Quaternary Ammonium Compounds (administration & dosage)
• Rats
• Rats, Inbred Lew
• Spleen (enzymology, immunology)
• T-Lymphocyte Subsets (immunology, metabolism, pathology)