LIGHT/HVEM/LTβR interaction as a target for the modulation of the allogeneic immune response in transplantation.
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.
Transplantation Immunobiology Section, Institute of Biomedicine, University of Leon, Leon, Spain.
M-L
ML
del Rio
P
P
Schneider
C
C
Fernandez-Renedo
J-A
JA
Perez-Simon
J-I
JI
Rodriguez-Barbosa
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D006084:Graft Rejection / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D053259:Lymphotoxin beta Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016377:Organ Transplantation; D011485:Protein Binding; D014184:Transplantation, Homologous; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000037:antagonists & inhibitors* / Q000276:immunology
D000911:Antibodies, Monoclonal; D053259:Lymphotoxin beta Receptor; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14