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Guiding regulatory T cells to the allograft

Lamarche, Caroline; Levings, Megan, K.

Current Opinion in Organ Transplantation: February 2018 - Volume 23 - Issue 1 - p 106–113
doi: 10.1097/MOT.0000000000000483
TOLERANCE INDUCTION: Edited by Maria-Luisa Alegre
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Purpose of review The application of regulatory T cell (Treg) therapy in organ transplantation is actively being pursued using unmodified, typically polyclonal cells. As the results of these ongoing clinical trials emerge, it is time to plan the next wave of clinical trials of Tregs. Here we will review a key strategy to improve Treg effectiveness and reduce side effects, namely increasing Treg specificity – both in terms of antigen recognition and localization to the allograft.

Recent findings Study of chemokine signatures accompanying acute rejection has revealed several chemokines that could be targeted to increase Treg homing. For example, Tregs possessing a Th1-like phenotype and expressing CXCR3 are better able to migrate towards local inflammation. Allografts themselves can be modified to increase Treg-attracting chemokines and Tregs themselves can produce chemokines, facilitating local proximity to their targets of suppression. Finally, tailoring Treg antigen specificity by T-cell or chimeric antigen receptor engineering is another approach to increase the specificity of suppression and optimize localization.

Summary Treg localization to the graft is important, but the important role of lymph node and germinal center homing cannot be overlooked. There is an opportunity to learn from advances made in cancer immunotherapy to optimize Treg therapy for transplantation.

Department of Surgery, University of British Columbia & British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada

Correspondence to Megan K. Levings, Department of Surgery, University of British Columbia, A4–186, 950 West 28th Avenue, Vancouver, BC, Canada V5Z4H4. Tel: +1 604 875 2000 ext 4686; fax:+1 604 875-2373; e-mail: mlevings@bcchr.ca

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