The role of regulatory T cells in the biology of graft versus host disease

Abstract

Graft versus host disease (GVHD) is the major complication of allogeneic hematopoietic stem cell transplantation. GVHD is characterized by an imbalance between the effector and regulatory arms of the immune system which results in the over production of inflammatory cytokines. Moreover, there is a persistent reduction in the number of regulatory T (Treg) cells which limits the ability of the immune system to re-calibrate this proinflammatory environment. Treg cells are comprised of both natural and induced populations which have unique ontological and developmental characteristics that impact how they function within the context of immune regulation. In this review, we summarize pre-clinical data derived from experimental murine models that have examined the role of both natural and induced Treg cells in the biology of GVHD. We also review the clinical studies which have begun to employ Treg cells as a form of adoptive cellular therapy for the prevention of GVHD in human transplant recipients.

Keywords: allogeneic stem cell transplantation; graft versus host disease; induced regulatory T cells; mouse models; regulatory T cells.

Figure 1

Proposed mechanism(s) of Treg cell suppression during GVHD. (A). nTreg cells migrate to secondary lymphoid tissues, where they prevent allorecognition by blocking the interaction between T cells and dendritic cells. (B,C) nTreg and iTreg cells inhibit T cell activation in the periphery by various mechanisms including cytokine deprivation, inhibitory receptors, and release of suppressive cytokines. (D) A subset of nTreg and iTreg cells lose Foxp3 expression and begin to secrete proinflammatory cytokines due to unknown environmental cues. The role of these cells in mediating pathological damage during GVHD is unknown. (This figure was created using Visi ScienceSlides^® Software).