| First Author | Zhai N | Year | 2023 |
| Journal | J Immunol | Volume | 211 |
| Issue | 5 | Pages | 885-894 |
| PubMed ID | 37486211 | Mgi Jnum | J:342475 |
| Mgi Id | MGI:7545440 | Doi | 10.4049/jimmunol.2200411 |
| Citation | Zhai N, et al. (2023) Lack of IFN-gamma Receptor Signaling Inhibits Graft-versus-Host Disease by Potentiating Regulatory T Cell Expansion and Conversion. J Immunol 211(5):885-894 |
| abstractText | IFN-gamma is a pleiotropic cytokine that plays a controversial role in regulatory T cell (Treg) activity. In this study, we sought to understand how IFN-gamma receptor (IFN-gammaR) signaling affects donor Tregs following allogeneic hematopoietic cell transplant (allo-HCT), a potentially curative therapy for leukemia. We show that IFN-gammaR signaling inhibits Treg expansion and conversion of conventional T cells (Tcons) to peripheral Tregs in both mice and humans. Mice receiving IFN-gammaR-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. In mice receiving Treg-depleted allo-HCT, IFN-gammaR deficiency-induced peripheral Treg conversion was effective in preventing persistent GVHD while minimally affecting GVL effects. Thus, impairing IFN-gammaR signaling in Tcons may offer a promising strategy for achieving GVL effects without refractory GVHD. Similarly, in a human PBMC-induced xenogeneic GVHD model, significant inhibition of GVHD and an increase in donor Tregs were observed in mice cotransferred with human CD4 T cells that were deleted of IFN-gammaR1 by CRISPR/Cas9 technology, providing proof-of-concept support for using IFN-gammaR-deficient T cells in clinical allo-HCT. |
