Journal
TRANSPLANT INTERNATIONAL
Volume 21, Issue 11, Pages 1015-1028Publisher
WILEY
DOI: 10.1111/j.1432-2277.2008.00726.x
Keywords
antigen-presenting cells; BTLA; CD160; co-inhibition; co-stimulation; HVEM; PD-1; PD-L1; PD-L2; peripheral tolerance; T cells; transplantation
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Funding
- Fondo de Investigaciones Sanitarias (Ministerio de Sanidad y Consumo, Spanish Government, Spain) [FIS 01-3026, FIS PI-050021]
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Transplantation of cells, tissues and vascularized solid organs is a successful therapeutic intervention for many end-stage chronic diseases. The combination of co-stimulatory blockade with the delivery of negative signals to T cells through co-inhibitory receptors would provide a robust approach to modulating T-cell receptor signaling and improving alloantigen-specific control of transplant rejection. This approach based on fundamental knowledge of APC/T-cell interactions may complement conventional therapies in the near future to reinforce long-term allograft survival, and permit minimal immunosuppression. The focus of this review was primarily on two major co-inhibitory signaling pathways, namely PD-1/PD-L1/PD-L2 and BTLA/CD160/HVEM/LIGHT that have been thoroughly characterized in murine models of transplantation using genetically modified mice, specific monoclonal antibodies and fusion proteins.
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