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

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• ELISpot and intracellular cytokine staining (ICS) are increasingly used in human immunodeficiency virus (HIV)-1 vaccine trials.
• These assays are often assumed to measure interferon-gamma (IFN-γ) secretion as a surrogate for T cell cytolytic activity.

Purpose of the Study:

• To determine if IFN-γ detection in CD8(+) T cells correlates with in vitro cytolytic ability.
• To compare the utility of ELISpot and ICS as surrogates for cytolytic assays.

Main Methods:

• Assessed virus-specific T cell responses in HIV-1-seronegative individuals using ELISpot, ICS, and chromium release ((51)Cr) assays.
• Analyzed responses to cytomegalovirus, Epstein-Barr virus, influenza, and HIV-1 Gag epitopes.
• Correlated results from different assay methods.

Main Results:

• Virus-specific T cell responses were detected in 69% of individuals.
• 18 (62.1%) of these individuals showed both IFN-γ secretion and cytolysis.
• Strong correlations were observed between IFN-γ ELISpot and ICS (ρ=0.88), and between (51)Cr release and ICS (ρ=0.81).

Conclusions:

• Intracellular cytokine staining (ICS) is a reliable surrogate for cytolytic assays in vaccine trials.
• ICS is superior to ELISpot for assessing T cell-mediated cytolysis.
• IFN-γ detection via ICS can effectively measure cytotoxic T lymphocyte activity.