Treg therapy in transplantation: a general overview

Abstract

Summary Solid organ transplantation remains the treatment of choice for end‐stage organ failure. Whilst the short‐term outcomes post‐transplant have improved in the last decades, chronic rejection and immunosuppressant side effects remain an ongoing concern. Hematopoietic stem cell transplantation is a well‐established procedure for the treatment of patients with haematological disorders. However, donor T cells are continually primed and activated to react against the host causing graft‐versus‐host disease (GvHD) that leads to tissue damages and death. Regulatory T cells (Tregs) play an essential role in maintaining tolerance to self‐antigens, preventing excessive immune responses and abrogating autoimmunity. Due to their suppressive properties, Tregs have been extensively studied for their use as a cellular therapy aiming to treat GvHD and limit immune responses responsible for graft rejection. Several clinical trials have been conducted or are currently ongoing to investigate safety and feasibility of Treg‐based therapy. This review summarizes the general understanding of Treg biology and presents the methods used to isolate and expand Tregs. Furthermore, we describe data from the first clinical trials using Tregs, explaining the limitations and future application of these cells.

Mitochondrial transfer from MSCs to T cells induces Treg differentiation and restricts inflammatory response

“…Since CD4 + CD25 + Foxp3 + Treg cells are critical in the control of tolerance and autoimmunity and also implicated in human diseases including GVHD [11], we used this model to assess ª 2020 The Authors EMBO reports 21: e48052 | 2020 human xenogeneic mouse model of GVHD (Fig 6A and B). Starting at 13 days post-GVHD induction, a significant difference in weight loss (P < 0.05) was observed comparing the PBMC-MitoT (88.5%) and control PBMC group (84.4%; Fig 6C).…”

Advances in the Use of Regulatory T-Cells for the Prevention and Therapy of Graft-vs.-Host Disease

“…Treg isolation using immunomagnetic beads is contaminated by effector T cells [26]. Several groups are exploring the use of Treg expansion protocols which include using the drug rapamycin to reduce the undesirable expansion of effector T cells and to increase the stability of the expanded Treg product [27].…”

“…Currently, these cells persistent on average 14 days following infusion [28]. Novel strategies combining Treg infusions with the immunosuppressive agent rapamycin or, more recently, low dose IL-2 are being investigated to prolong Treg survival and increase Treg stability in vivo [26]. There is also a need for further studies looking into the generation of “off the shelf” Treg cellular products.…”

Dosing optimization of CCR4 immunotoxin for improved depletion of CCR4+ Treg in nonhuman primates

“…Tregs suppress abnormal immune response against self‐antigen and also suppress antitumor immune response. Treg depletion or induction is a new therapeutic strategy for treating various diseases including autoimmune diseases, cancers, and transplantation tolerance induction (Hall, ; Liu et al ., ; Lu et al ., ; Romano et al ., ; Tanaka and Sakaguchi, ). Chemokine (C‐C motif) receptor 4 (CCR4) is recognized as an important effector Treg target (Sugiyama et al ., ).…”