Anti-T Lymphocyte Globulin (ATG) Induces Generation of Regulatory T Cells, at Least Part of Them Express Activated CD44

Abstract

We show here that the anti-T lymphocyte immunoglobulin (ATG) can induce Treg cells following 24-h incubation in human peripheral blood mononuclear cells (PBMCs). The ATG-induced Treg cells express known cell surface markers (e.g., CD25, FoxP3) and suppress the proliferation of autologous responder PBMCs, stimulated with allogeneic PBMCs, when added into the mixed lymphocyte culture (MLC) at zero time point or 48 h later. We expanded the characteristics of the ATG-induced human Treg cells by showing that they express a novel biomarker designated "activated CD44". ATG-induced Treg cells retain their suppressor function after freezing and thawing or irradiation. Suppression of MLC by ATG-induced Treg cells is consistently seen when the Treg cells and the responder cells were derived from the same donor, but not when they derived from different donors. Finally, patients undergoing stem cell transplantation and conditioned with ATG generate in vivo Treg cells that suppress MLC.

Effective prevention of GVHD using in vivo T-cell depletion with anti-lymphocyte globulin in HLA-identical or -mismatched sibling peripheral blood stem cell transplantation

“…Another potential ATG for HLA-identical or -mismatched sibling transplantation C Wolschke et al effect is the induction of regulatory T cells. 21 We did not observe a higher risk of infection-related death in the ATG group, and there was only a trend for a higher CMV reactivation in the ATG group. However, we observed a higher EBV reactivation in the ATG group.…”

Intrinsic impairment of CD4+CD25+ regulatory T cells in acquired aplastic anemia

“…Logically, a Treg-enhanced immunosuppressive strategy might alleviate the disease severity and be beneficial to improve hematopoietic recovery, which was supported by the fact that antithymocyte globulin could promote expansion of functional Tregs in vitro. 41,42 In addition, Tregs from AA patients had less capacity to suppress proliferation and cytokine production by autologous effector T. Our study provided strong evidence that the impaired Treg-mediated immunosuppression was because of intrinsic defects in Tregs, rather than resistance of effector T cells. We herein speculated that it was the impaired Tregs (but not for effector T cells) that played a more critical role in the pathophysiology of AA.…”

Anti-thymocyte globulin as graft- versus -host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…27 Furthermore, rabbit (but not horse) ATG induces the generation of regulatory T cells (Treg), both in vitro and in vivo. [31][32][33] This is clinically relevant given accumulating evidence showing an important role for Treg in GvHD prevention after allogeneic HCT. [34][35][36][37] The next paragraphs review the impact of both forms of rabbit ATG on transplantation outcomes in various transplantation settings.…”