CD150highTreg cells may attenuate graft versus host disease and intestinal cell apoptosis after hematopoietic stem cell transplantation

Am J Transl Res. 2019 Mar 15;11(3):1299-1310. eCollection 2019.

Abstract

Combined transplantation of regulatory T cells (Treg cells) may significantly attenuate graft versus host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Recent studies indicated that CD150+Treg cells could secret adenosine to maintain the quiescent status of HSCs. However, whether it is attributable to the attenuation of GVHD after HSCT is still unclear. In vitro studies revealed that CD150+Treg cells induced immune tolerance was comparable to that induced by CD150-Treg cells, but CD150+Treg cells can secret more adenosine, increase P-AMPK expression and regulate energy metabolism to induce the proliferation of HSC proliferation and inhibit their differentiation into dendritic cells. In this study, GVHD animal model was established, and combined transplantation of Treg cells and HSCs was performed. Results showed the survival time was significantly prolonged, the proliferation rate of HSCs increased significantly and the proportion of undifferentiated HSCs elevated significantly after CD150+Treg transplantation as compared to CD150-Treg transplantation. Immunohistochemistry revealed CD150+Treg cells could secret adenosine, activate AMPK expression and inhibit intestinal cell apoptosis and inflammation after HSCT. Taken together, this study indicates CD150+Treg cells can regulate energy metabolism to attenuate GVHD and intestinal cell apoptosis after HSCT.

Keywords: CD150; Regulatory T cells; energy metabolism; graft versus host disease; hematopoietic stem cell transplantation.