Correlation between interferon- gamma secretion and cytotoxicity, in virus-specific memory T cells.
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.
Horton
Helen
H
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Russell
Nina
N
Moore
Erin
E
Frank
Ian
I
Baydo
Ruth
R
Havenar-Daughton
Colin
C
Lee
Deborah
D
Deers
Mark
M
Hudgens
Michael
M
Weinhold
Kent
K
McElrath
M Juliana
MJ
D000956:Antigens, Viral / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D003587:Cytomegalovirus / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D006678:HIV / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000032:analysis* / Q000378:metabolism; D009975:Orthomyxoviridae / Q000276:immunology; D013194:Staining and Labeling / Q000379:methods; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000956:Antigens, Viral; D015415:Biomarkers; D007371:Interferon-gamma