Correlation between interferon- gamma secretion and cytotoxicity, in virus-specific memory T cells

J Infect Dis. 2004 Nov 1;190(9):1692-6. doi: 10.1086/424490. Epub 2004 Sep 30.


ELISpot and intracellular cytokine staining are replacing the traditional cytolytic ((51)Cr release) assay method in vaccine trials using human immunodeficiency virus (HIV)-1, and it is widely assumed that the number of interferon (IFN)- gamma -secreting T cells is a surrogate for the level of cytolytic activity. Thus, we sought to determine whether the detection of IFN- gamma in CD8(+) T cells correlates with cytolytic ability in vitro. In 29 (69.0%) of 42 HIV-1-seronegative immunocompetent individuals (22 unvaccinated and 20 vaccinated), virus-specific T cell responses recognizing cytomegalovirus, Epstein-Barr virus, and influenza and HIV-1 Gag epitopes were detected by at least 1 assay method (ELISpot, intracellular cytokine staining, and/or (51)Cr release), and 18 (62.1%) of these 29 demonstrated both IFN- gamma secretion and cytolysis. There was strong correlation between the results of IFN- gamma ELISpot and those of IFN- gamma intracellular cytokine staining ( rho =0.88) and between the results of (51)Cr release and those of intracellular cytokine staining ( rho =0.81); although the correlation is not absolute, intracellular cytokine staining can be used--and is superior to ELISpot--as a surrogate for cytolytic assays.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Viral / immunology
  • Biomarkers / analysis
  • Cytomegalovirus / immunology
  • Cytotoxicity Tests, Immunologic
  • Cytotoxicity, Immunologic*
  • HIV / immunology
  • Herpesvirus 4, Human / immunology
  • Humans
  • Immunologic Memory*
  • Interferon-gamma / analysis*
  • Interferon-gamma / metabolism
  • Orthomyxoviridae / immunology
  • Staining and Labeling / methods
  • T-Lymphocytes, Cytotoxic / immunology*


  • Antigens, Viral
  • Biomarkers
  • Interferon-gamma