title: Transplantation tolerance: context matters.
abstract: Costimulation blockade has been one of the most studied strategies to achieve immune tolerance, particularly in transplantation. Yet, in spite of the robust nature of the tolerance-inducing potential of costimulation blockade, a comprehensive understanding of the molecular and cellular mechanisms underlying tolerance induction is still missing. Nevertheless, progress has been continuously made. In this issue of the European Journal of Immunology, Chai et al. [Eur. J. Immunol. 2015. 45: 2017-2027] show that transplantation tolerance induced with an anti-CD154 monoclonal antibody relies on the coexistence of several tolerogenic mechanisms rather than one simple regulatory mechanism. These observations highlight the importance of concerted actions involving multiple pathways, namely apoptosis, acquisition of regulatory cells, or inhibition of proliferation, all of which contribute to the induction and maintenance of robust immune tolerance. A better understanding of these distinct tolerogenic pathways may lead to the development of better tolerance-inducing therapeutics.
authors.affiliation: Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.|Instituto Gulbenkian de Ciências, Oeiras, Portugal.
authors.forename: Luis
authors.initials: L
authors.lastname: Graca
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D006801:Humans; D023001:Transplantation Tolerance / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal
keywords: Activation-induced cell death; CD154; Costimulation blockade; Donor-specific transfusion; Regulatory T cells; Transplantation tolerance