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

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.