Journal
FRONTIERS IN IMMUNOLOGY
Volume 6, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2015.00242
Keywords
immunotherapy; tolerance; monoclonal antibodies; depletion; Foxp3(+) Tregs; resistance; CD3
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Funding
- RISET consortium (Reprogramming the Immune System for the Establishment of Tolerance) from the European Commission (FP6) [512090]
- Juvenile Diabetes Research Foundation (JDRF) [1-2011-654]
- Fondation CENTAURE
- INSERM
- University Paris Descartes
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Despite significant progress achieved in transplantation, immunosuppressive therapies currently used to prevent graft rejection are still endowed with severe side effects impairing their efficiency over the long term. Thus, the development of graft-specific, non-toxic innovative therapeutic strategies has become a major challenge, the goal being to selectively target alloreactive effector T cells while sparing CD4(+)Foxp3(+) regulatory T cells (Tregs) to promote operational tolerance. Various approaches, notably the one based on monoclonal antibodies or fusion proteins directed against the TCR/CD3 complex, TCR coreceptors, or costimulatory molecules, have been proposed to reduce the alloreactive T cell pool, which is an essential prerequisite to create a therapeutic window allowing Tregs to induce and maintain allograft tolerance. In this mini review, we focus on the differential sensitivity of Tregs and effector T cells to the depleting and inhibitory effect of these immunotherapies, with a particular emphasis on CD3-specific antibodies that beyond their immunosuppressive effect, also express potent tolerogenic capacities.
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