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CD40/CD154 interactions at the interface of tolerance and immunity

Quezada, SA; Jarvinen, LZ; Lind, EE; Noelle, RJ; (2004) CD40/CD154 interactions at the interface of tolerance and immunity. ANNU REV IMMUNOL , 22 307 - 328. 10.1146/annurev.immunol.22.012703.104533.

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Abstract

Development of the acquired immune response is dependent on the signaling of CD40 by its ligand, CD 154. These molecules govern both the magnitude and quality of humoral- and cell-mediated immunity. A litany of studies have conclusively documented that blockade of this ligand-receptor pair can prevent, and also intervene in, the progression of antibody- and cell-mediated autoimmune diseases, and can instill long-lived allogeneic and xenogeneic graft tolerance. Many effector mechanisms of inflammation are abolished as a result of CD 154 blockade, but we are now beginning to understand that CD 154 blockade may, in some instances, engender long-lived, antigen-specific tolerance. In the context of transplantation tolerance, we present a hypothesis that alphaCD154 blockade is most effective at inducing long-lived allospecific tolerance if anergy and regulation can be elicited prior to the onslaught of inflammation that is induced by grafting (preemptive tolerance). This facet of alphaCD154-induced tolerance appears to co-opt the normal processes of peripheral tolerance induced by immature DCs and can be exploited to induce long-lived antigen-specific tolerance. The underlying science and the prospects for inducing long-lived antigen- specific tolerance in a model of allograft tolerance through CD154 blockade are presented and discussed.

Type: Article
Title: CD40/CD154 interactions at the interface of tolerance and immunity
DOI: 10.1146/annurev.immunol.22.012703.104533
Keywords: immature dendritic cell, transplantation tolerance, suppressor, donor transfusion, cell-mediated immunity, REGULATORY T-CELLS, NF-KAPPA-B, IMMUNOLOGICAL SELF-TOLERANCE, DONOR-SPECIFIC TRANSFUSION, IMMATURE DENDRITIC CELLS, SYSTEMIC-LUPUS-ERYTHEMATOSUS, TUMOR-NECROSIS-FACTOR, EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, INFECTIOUS TRANSPLANTATION TOLERANCE, ANTI-CD154 MONOCLONAL-ANTIBODY
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/1298247
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