Monoclonal Antibody Specific for TIRC7 Induces Donor-specific Anergy and Prevents Rejection of Cardiac Allografts in Mice

2004/04/01 by Yusuke Kumamoto, Antje Tomschegg, Fatima Bennai-Sanfourche +8 · 22 citations
Immunology and Microbiology · Medicine · #T-cell and B-cell Immunology #Immune Cell Function and Interaction #Immune Response and Inflammation #Medicine #Monoclonal antibody #Immunology #Immune system #Transplantation #T cell #Tumor necrosis factor alpha #Lymphocyte #Ex vivo #IL-2 receptor #In vivo #Mixed lymphocyte reaction #Interleukin 2 #T lymphocyte #Cancer research #Antibody #Biology #Internal medicine

paper · pdf · doi:10.1111/j.1600-6143.2004.00367.x

published in American Journal of Transplantation 4(4), 505-514 (Elsevier BV)

openalex publication_date 2004/04/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06

Abstract

T cell immune response c-DNA (TIRC7) is up-regulated during the early stages of T-cell activation in response to alloantigens. In this study, we analyzed the effects of newly developed monoclonal antibodies (mAb) against TIRC7 in acute cardiac allograft rejection. Fully vascularized heterotopic allogeneic heart transplantation was performed in mice across a full-mismatch barrier (C57Bl/10 into CBA). Recipients received seven injections (day 0-7) of a novel anti-TIRC7 mAb or remained untreated. Graft survival, histology and ex vivo lymphocyte functions were tested. Targeting of TIRC7 with an anti-TIRC7 mAb diminishes lymphocyte infiltration into grafts resulting in delay of morphological graft damage and prolongation of allograft survival. The lymphocytes from anti-TIRC7 mAb-treated animals exhibit hypo-responsiveness without evidence of lymphocyte depletion against the donor allo-antigens. Proliferation and expression of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) were down-regulated while interleukin-4 (IL-4) and IL-10 expression were spared. Moreover, anti-TIRC7 mAb enhanced up-regulation of CTLA-4 expression but suppressed up-regulation of CD25 on stimulated lymphocytes in vitro and in vivo. Ligation of TIRC7 has important effects on the regulation of co-stimulatory signaling pathways associated with suppressing of T-cell activation. Targeting of TIRC7 may therefore provide a novel therapeutic approach for modulating T cell immune responses during organ transplantation.

Citations

• Monitoring of intragraft and peripheral blood TIRC7 expression as a diagnostic tool for acute cardiac rejection in humans
• Prevention of Acute Allograft Rejection by Antibody Targeting of TIRC7, a Novel T Cell Membrane Protein
• Genomic Organization of the Gene Coding for TIRC7, a Novel Membrane Protein Essential for T Cell Activation
• CD40 AND CD154 IN CELL-MEDIATED IMMUNITY
• Immunologic Self-Tolerance Maintained by Cd25+Cd4+Regulatory T Cells Constitutively Expressing Cytotoxic T Lymphocyte–Associated Antigen 4

Cited by

• Antibody targeting of TIRC7 results in significant therapeutic effects on collagen-induced arthritis in mice
• Prediction of Graft-Versus-Host Disease in Humans by Donor Gene-Expression Profiling
• HLA-DR Alpha 2 Mediates Negative Signalling via Binding to Tirc7 Leading to Anti-Inflammatory and Apoptotic Effects in Lymphocytes In Vitro and In Vivo
• TIRC7 and HLA-DR axis contributes to inflammation in multiple sclerosis
• TIRC7 Deficiency Causes In Vitro and In Vivo Augmentation of T and B Cell Activation and Cytokine Response
• TIRC7 Inhibits T Cell Proliferation by Modulation of CTLA-4 Expression
• TCIRG1 [wikipedia]