T cell–dependent production of IFN-γ by NK cells in response to influenza A virus
Xiao-Song He, Monia Draghi, Kutubuddin Mahmood, Tyson H. Holmes, George W. Kemble, Cornelia L. Dekker, Ann M. Arvin, Peter Parham, Harry B. Greenberg
Xiao-Song He, Monia Draghi, Kutubuddin Mahmood, Tyson H. Holmes, George W. Kemble, Cornelia L. Dekker, Ann M. Arvin, Peter Parham, Harry B. Greenberg
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Article Immunology

T cell–dependent production of IFN-γ by NK cells in response to influenza A virus

Abstract

The role of human NK cells in viral infections is poorly understood. We used a cytokine flow-cytometry assay to simultaneously investigate the IFN-γ response of NK and T lymphocytes to influenza A virus (fluA). When PBMCs from fluA-immune adult donors were incubated with fluA, IFN-γ was produced by both CD56dim and CD56bright subsets of NK cells, as well as by fluA-specific T cells. Purified NK cells did not produce IFN-γ in response to fluA, while depletion of T lymphocytes reduced to background levels the fluA-induced IFN-γ production by NK cells, which indicates that T cells are required for the IFN-γ response of NK cells. The fluA-induced IFN-γ production of NK cells was suppressed by anti–IL-2 Ab, while recombinant IL-2 replaced the helper function of T cells for IFN-γ production by NK cells. This indicates that IL-2 produced by fluA-specific T cells is involved in the T cell–dependent IFN-γ response of NK cells to fluA. Taken together, these results suggest that at an early stage of recurrent viral infection, NK-mediated innate immunity to the virus is enhanced by preexisting virus-specific T cells.

Authors

Xiao-Song He, Monia Draghi, Kutubuddin Mahmood, Tyson H. Holmes, George W. Kemble, Cornelia L. Dekker, Ann M. Arvin, Peter Parham, Harry B. Greenberg

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FluA-induced IFN-γ production by the CD3–CD56bright perforin– NK cell su...
FluA-induced IFN-γ production by the CD3–CD56bright perforin– NK cell subset (labeled as CD56bright) and CD3–CD56dim perforin+ NK cell subset (labeled as CD56dim) in 25 donors. PBMCs were incubated with fluA for 17 hours, followed by cytokine flow-cytometric analysis (see Methods). Lines connect pairs of observations from the same donor. Black bars mark the positions of groups’ means, which were compared using paired Student’s t tests. The attained significance levels (P values) are reported. For A and C, the t tests were performed on logarithmic-transformed data. (A) The percentage of IFN-γ+ cells in the 2 NK cell subsets. (B) The IFN-γ MFI of IFN-γ+ cells in the 2 NK cell subsets. (C) The total numbers of IFN-γ+ cells detected simultaneously in the 2 NK cell subsets from the same PBMC aliquot of each donor.