Harnessing Advances in T Regulatory Cell Biology for Cellular Therapy in Transplantation.

Cellular therapy with CD4+FOXP3+ T regulatory cells (Treg) is a promising strategy to induce tolerance after solid-organ transplantation or prevent graft-versus-host disease after transfer of hematopoietic stem cells. Tregs currently used in clinical trials are either polyclonal, donor- or antigen-specific. Aside from variations in isolation and expansion protocols, however, most therapeutic Treg cell-based products are much alike. Ongoing basic-science work has provided considerable new insight into multiple facets of Treg biology, including their stability, homing, and functional specialization; integrating these basic-science discoveries with clinical efforts will support the development of next-generation therapeutic Tregs with enhanced efficacy. In this review, we summarize recent advances in knowledge of how Tregs home to lymphoid and peripheral tissues, and control antibody production and tissue repair. We also discuss newly appreciated pathways that modulate context-specific Treg function and stability. Strategies to improve and tailor Tregs for cell therapy to induce transplantation tolerance are highlighted. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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