LIGHT/HVEM/LTβR Interaction as a Target for the Modulation of the Allogeneic Immune Response in Transplantation |
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| Authors: | M.‐L. del Rio P. Schneider C. Fernandez‐Renedo J.‐A. Perez‐Simon J.‐I. Rodriguez‐Barbosa |
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| Affiliation: | 1. Transplantation Immunobiology Section, Institute of Biomedicine, University of Leon, , Leon, Spain;2. Castilla and Leon Regional Transplantation Coordination, Leon University Hospital, , Leon, Spain;3. Department of Biochemistry, University of Lausanne, , CH‐1066 Epalinges, Switzerland;4. Department of Hematology, Virgen del Rocio University Hospital and Institute of Biomedicine (IBIS), , Sevilla, Spain |
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| Abstract: | The exchange of information during interactions of T cells with dendritic cells, B cells or other T cells regulates the course of T, B and DC‐cell activation and their differentiation into effector cells. The tumor necrosis factor superfamily member LIGHT (homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for binding to herpesvirus entry mediator, a receptor expressed on T lymphocytes) is transiently expressed upon T cell activation and modulates CD8 T cell‐mediated alloreactive responses upon herpes virus entry mediator (HVEM) and lymphotoxin β receptor (LTβR) engagement. LIGHT‐deficient mice, or WT mice treated with LIGHT‐targeting decoy receptors HVEM‐Ig, LTβR‐Ig or sDcR3‐Ig, exhibit prolonged graft survival compared to untreated controls, suggesting that LIGHT modulates the course and severity of graft rejection. Therefore, targeting the interaction of LIGHT with HVEM and/or LTβR using recombinant soluble decoy receptors or monoclonal antibodies represent an innovative therapeutic strategy for the prevention and treatment of allograft rejection and for the promotion of donor‐specific tolerance. |
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| Keywords: | Coinhibition costimulation HVEM LIGHT LTβ R transplantation |
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