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.

Donor-Derived Regulatory T Cells Attenuate the Severity of Acute Graft-Versus-Host Disease after Cord Blood Transplantation

“…+ FoxP3 + T regs detected in CD4 + ATs Tregs have been found to exert vital functions in restricting aGVHD by suppressing the proliferation or induce the apoptosis of Teffs (Beres and Drobyski 2013). It remains controversial whether CB contains a larger number of natural Tregs (nTregs) than APB.…”

New agents in HSC mobilization

“…The transplant of blood mobilized using CDX-301 plus AMD3100 into lethally ablated mice was also shown to be associated with a survival advantage [74]. Moreover, the CDX-301 plus AMD3100 combination effectively mobilized regulatory T cells (T reg ), which may have protective effects against graft vs host disease (GvHD) after allogeneic transplantation (Reviewed in [75]). Indeed, transplantation of irradiated recipients with blood mobilized with CDX-301, either alone or in combination with AMD3100 correlated with enhanced survival in an allogeneic transplant setting [74].…”

AFM detection of biophysical characteristics of specific regulatory T Cells after allogeneic hematopoietic stem cell transplantation

“…Graft versus host disease (GVHD) is the main complications following allo-HSCT. GVHD is primarily a donor T cellmediated syndrome whereby T cells in the graft elicit an immune response, resulting in host tissue damage [1,2]. Knowledge of the immunobiology underlying GVHD has advanced by virtue of immunology research in animal models, as well as clinical observations.…”

“…Since GVHD is characterized by the loss of tolerance and the development of autoimmune manifestations, it is reasonable to indicate that a deficiency in regulatory T (Treg) cells reconstitution plays a critical role in GVHD pathophysiology and might participate in mediating GVHD and graft-versus-leukemia (GVL) effect after allo-HSCT [4,5]. The Treg cells, which identified suppressive population of CD4+ T cells that expressed high levels of the IL-2 receptor α-chain (CD25) formerly known as suppressor T cells, are a subpopulation of T cells which modulate the immune system, maintain tolerance to self-antigens, and abrogate autoimmune disease [1,6,7]. Mouse models have suggested that modulation of Treg cells can treat autoimmune disease and cancer, and facilitate organ transplantation [1,3,8], while the molecular mechanism of Treg cells is still unclear.…”