Defining a TCF1-expressing progenitor allogeneic CD8+ T cell subset in acute graft-versus-host disease

Abstract Graft-versus-host disease (GvHD) is a severe complication of hematopoietic stem cell transplantation driven by activated allogeneic T cells. Here, we identify a distinct subset of T cell factor-1 (TCF1)+ CD8+ T cells in mouse allogeneic and xenogeneic transplant models of acute GvHD. These TCF1+ cells exhibit distinct characteristics compared to TCF1- cells, including lower expression of inhibitory receptors and higher expression of costimulatory molecules. Notably, the TCF1+ subset displays exclusive proliferative potential and could differentiate into TCF1- effector cells upon antigenic stimulation. Pathway analyses support the role of TCF1+ and TCF1- subsets as resource cells and effector cells, respectively. Furthermore, the TCF1+ CD8+ T cell subset is primarily present in the spleen and exhibits a resident phenotype. These findings provide insight into the differentiation of allogeneic and xenogeneic CD8+ T cells and have implications for the development of immunotherapeutic strategies targeting acute GvHD.