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.