Gamma interferon expression in CD8⁺ T cells is a marker for circulating cytotoxic T lymphocytes that recognize an HLA a2-restricted epitope of human cytomegalovirus phosphoprotein pp65

Antigen-specific CD8⁺ T cells with cytotoxic activity are often critical in immune responses to infectious pathogens. To determine whether gamma interferon (IFN-γ) expression is a surrogate marker for cytotoxic T lymphocytes (CTL), human cytomegalovirus-specific CTL responses were correlated with CD8⁺ T-cell IFN-γ expression determined by cytokine flow cytometry. A strong positive correlation was observed between specific lysis of peptide-pulsed targets in a ⁵¹Cr release assay and frequencies of peptide-activated CD8⁺ T cells expressing IFN-γ at 6 h (r² = 0.72) or 7 days (r² = 0.91). Enumeration of responding cells expressing perforin, another marker associated with CTL, did not improve this correlation. These results demonstrate that IFN-γ expression can be a functional surrogate for identification of CTL precursor cells.