Naicui Zhai, Wentao Liu, Chun-Hui Jin, Yanan Ding, Liguang Sun, Donghui Zhang, Zhaowei Wang, Yang Tang, Wenjie Zhao, Christian LeGuern, Markus Y Mapara, Hui Wang, Yong-Guang Yang
IFN-γ is a pleiotropic cytokine that plays a controversial role in regulatory T cell (Treg) activity. In this study, we sought to understand how IFN-γ receptor (IFN-γR) signaling affects donor Tregs following allogeneic hematopoietic cell transplant (allo-HCT), a potentially curative therapy for leukemia. We show that IFN-γR signaling inhibits Treg expansion and conversion of conventional T cells (Tcons) to peripheral Tregs in both mice and humans. Mice receiving IFN-γR-deficient allo-HCT showed markedly reduced graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects, a trend associated with increased frequencies of Tregs, compared with recipients of wild-type allo-HCT...
July 24, 2023: Journal of Immunology