Antibody targeting of TIRC7 results in significant therapeutic effects on collagen-induced arthritis in mice

Clin Exp Immunol. 2006 Apr;144(1):142-51. doi: 10.1111/j.1365-2249.2006.03044.x.

Abstract

TIRC7 is a cell surface molecule which is expressed in T and B lymphocytes and negatively regulates their function. Anti-TIRC7 specific monoclonal antibody (mAb) inhibited T cell memory response to recall antigens. Up-regulation of TIRC7 on lymphocytes from joint tissue of patients with Rheumatoid Arthritis (RA) and mice with collagen induced arthritis (CIA) suggested TIRC7 as a novel target to promote anti-inflammatory reaction. Anti-TIRC7 mAb administration significantly inhibited the induction and progression of CIA and the anti-collagen IgG1 and IgG2a antibody response. Combination therapy of anti-TIRC7 mAb and soluble TNF-alpha receptor demonstrated an increased inhibitory effect over the single compounds on CIA. The results demonstrate the therapeutic potential of TIRC7 targeting with mAb in diseases associated with exaggerated T and B cell responses.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / therapy
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / therapy
  • B-Lymphocytes / immunology
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Immunologic Memory / immunology
  • Immunotherapy / methods
  • Knee Joint / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Receptors, Tumor Necrosis Factor / immunology
  • Synovial Fluid / immunology
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / immunology
  • Up-Regulation / immunology
  • Vacuolar Proton-Translocating ATPases / immunology*

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • TCIRG1 protein, human
  • Tumor Necrosis Factor-alpha
  • Vacuolar Proton-Translocating ATPases