This study identifies a unique population of virus-specific CD8+ T cells that proliferate after blockade of the PD-1 inhibitory pathway in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). These LCMV-specific CD8+ T cells express the PD-1 inhibitory receptor but also several costimulatory molecules such as ICOS and CD28. This subset, characterized by a unique gene signature, resembles CD4+ T follicular helper (T<FH> cells), CD8+ memory precursor cells, and hematopoietic stem cell progenitors. These CXCR5+ CD8+ T cells are found only in lymphoid tissues and reside predominantly in the T cell zones along with naïve CD8+ T cells. They undergo self-renewal and differentiate into terminally exhausted CD8+ T cells present in both lymphoid and non-lymphoid tissues. The proliferative burst after PD-1 blockade primarily comes from this CXCR5+ CD8+ T cell subset, which is regulated by the transcription factor TCF1. These findings provide insights into T cell exhaustion and have implications for optimizing PD-1-directed immunotherapy in chronic infections and cancer.This study identifies a unique population of virus-specific CD8+ T cells that proliferate after blockade of the PD-1 inhibitory pathway in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). These LCMV-specific CD8+ T cells express the PD-1 inhibitory receptor but also several costimulatory molecules such as ICOS and CD28. This subset, characterized by a unique gene signature, resembles CD4+ T follicular helper (T<FH> cells), CD8+ memory precursor cells, and hematopoietic stem cell progenitors. These CXCR5+ CD8+ T cells are found only in lymphoid tissues and reside predominantly in the T cell zones along with naïve CD8+ T cells. They undergo self-renewal and differentiate into terminally exhausted CD8+ T cells present in both lymphoid and non-lymphoid tissues. The proliferative burst after PD-1 blockade primarily comes from this CXCR5+ CD8+ T cell subset, which is regulated by the transcription factor TCF1. These findings provide insights into T cell exhaustion and have implications for optimizing PD-1-directed immunotherapy in chronic infections and cancer.