Interpretation of transplant biopsies and immune responses following Treg cell therapy

Abstract

Purpose of review Regulatory T cells (Treg) are now well established as vital participants in maintaining self tolerance and preventing autoimmunity. Tregs have already been shown to be effective in preventing graft-versus-host disease in clinical bone marrow transplantation, and numerous animal studies have suggested a therapeutic role for Treg in solid organ transplantation. Recent advances in Treg isolation and expansion have the field poised to perform trials of therapeutic Treg infusion in solid organ transplantation around the world. An important component of these trials will be the detection of infused cells and the assessment Treg activity after infusion. Recent findings Several animal studies have demonstrated that infused Treg migrate to transplanted tissue in the early period after transplantation. This finding has important implications for the interpretation of biopsy results in human trials. Recent refinements in Treg identification, quantification, and functional assays will be discussed in the context of immune monitoring. Summary Understanding the migration/localization and persistence of infused Treg into transplanted tissues as well as how they impact the peripheral immune response will be critical to the interpretation of early Treg trials.

C5a Blockade Increases Regulatory T Cell Numbers and Protects Against Microvascular Loss and Epithelial Damage in Mouse Airway Allografts

“…The association between the complement pathway and Tregs has been well reported ( 59 ). Tregs play a crucial role in maintaining immune tolerance in both preclinical studies and are also associated with improved long-term transplant outcomes in clinical studies ( 60 , 61 ).…”

Global Regulatory T-Cell Research from 2000 to 2015: A Bibliometric Analysis

“…Although the first studies focused on the inhibition of effector T-cell (Teff) priming by Tregs in secondary lymphoid organs, it has been reported that the Treg response adapts to the immune response (i.e., Th1, Th17, Th2, and Tfh cells), and that Tregs show further specialization in peripheral tissues via tissue repair and homeostasis [ 3 – 6 ]. In animal models, Tregs play a central role in promoting and maintaining allograft tolerance [ 7 – 9 ]. Kim and Lahl et al [ 10 , 11 ] demonstrated that Tregs participate in the maintenance of immune self-tolerance and homeostasis.…”

Treg Therapy in Transplantation: How and When Will We Do It?

“…Tregs represent less than 10 % of CD4 + T cells, which therefore make up about 13×10 9 cells in the whole body [56]. A ratio of Tregs to effector T cells of 1:3 showed a positive outcome in biopsies of rats [57]. Lower ratios were more connected to rejection.…”

“…From studies in animal models, we know that the best effect is observed when Tregs are given in a prophylactic manner prior to or at the time of transplantation [5,7,57,63]. Here, the aim is to prevent acute rejection of allogeneic transplants and to induce tolerance very often without concomitant use of other immunomodulatory agents.…”