CXCR5+CD8+ T cells arise in response to protein immunization and peripheral viral infection, displaying a follicular-homing phenotype, expression of cell surface molecules associated with Tfh cells and limited cytotoxic potential. CXCR5+ CD8+ T cells shape the antibody response to protein immunization and peripheral viral infection, promoting class switching to IgG2c in responding B cells. This evidence concerns the gene CXCR5 and viral infectious disease.