This study identifies a unique population of CD8⁺ T cells that proliferate after PD-1 pathway blockade in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). These cells express PD-1 and several costimulatory molecules, including ICOS and CD28, and have a gene signature similar to CD4⁺ T follicular helper (TFH) cells, CD8⁺ memory precursors, and hematopoietic stem cell progenitors. They are found predominantly in lymphoid tissues, particularly in the T cell zones, and resemble stem cells during chronic infection, undergoing self-renewal and differentiating into terminally exhausted CD8⁺ T cells. The proliferative burst after PD-1 blockade comes almost exclusively from this CD8⁺ T cell subset. The transcription factor TCF1 plays a cell intrinsic and essential role in the generation of this CD8⁺ T cell subset. These findings provide a better understanding of T cell exhaustion and have implications for optimizing PD-1-directed immunotherapy in chronic infections and cancer. The study also shows that these CD8⁺ T cells are distinct from other exhausted CD8⁺ T cells and have a unique transcriptional program, which may represent a specific adaptation of CD8⁺ T cells to chronic antigenic stimulation. The identification of these cells has implications for understanding immune responses in autoimmunity and cancer. The study highlights the importance of PD-1 pathway blockade in restoring function in exhausted CD8⁺ T cells and improving immunotherapy outcomes in chronic infections and cancer.This study identifies a unique population of CD8⁺ T cells that proliferate after PD-1 pathway blockade in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). These cells express PD-1 and several costimulatory molecules, including ICOS and CD28, and have a gene signature similar to CD4⁺ T follicular helper (TFH) cells, CD8⁺ memory precursors, and hematopoietic stem cell progenitors. They are found predominantly in lymphoid tissues, particularly in the T cell zones, and resemble stem cells during chronic infection, undergoing self-renewal and differentiating into terminally exhausted CD8⁺ T cells. The proliferative burst after PD-1 blockade comes almost exclusively from this CD8⁺ T cell subset. The transcription factor TCF1 plays a cell intrinsic and essential role in the generation of this CD8⁺ T cell subset. These findings provide a better understanding of T cell exhaustion and have implications for optimizing PD-1-directed immunotherapy in chronic infections and cancer. The study also shows that these CD8⁺ T cells are distinct from other exhausted CD8⁺ T cells and have a unique transcriptional program, which may represent a specific adaptation of CD8⁺ T cells to chronic antigenic stimulation. The identification of these cells has implications for understanding immune responses in autoimmunity and cancer. The study highlights the importance of PD-1 pathway blockade in restoring function in exhausted CD8⁺ T cells and improving immunotherapy outcomes in chronic infections and cancer.