T cell–dependent production of IFN-γ by NK cells in response to influenza A virus
Xiao-Song He, … , Peter Parham, Harry B. Greenberg
Xiao-Song He, … , Peter Parham, Harry B. Greenberg
Published December 15, 2004
Citation Information: J Clin Invest. 2004;114(12):1812-1819. https://doi.org/10.1172/JCI22797.
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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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Figure 1

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IFN-γ production by T cells and CD56dim and CD56bright NK cell subsets i...
IFN-γ production by T cells and CD56dim and CD56bright NK cell subsets in response to fluA. PBMCs from an adult donor were incubated with fluA (A–F) or SPG (negative control, G and H) for 17 hours, with brefeldin A added during the last 5 hours. The cells were stained for CD56, fixed and permeabilized, and then stained for CD3, IFN-γ, and perforin. See Methods for details. Displayed in the dot plots A–H are cells gated on different lymphocyte populations: (A) IFN-γ production of CD3– and CD3+ lymphocytes (gated by forward scattering and side scattering) in response to fluA; (B) IFN-γ production of CD3+ lymphocytes in response to fluA; (C) IFN-γ production of CD3– lymphocytes in response to fluA; (D) expression of CD56 and perforin by CD3– lymphocytes; (E and F) IFN-γ production of CD56dim perforin+ NK and CD56bright perforin– NK subsets, respectively, in response to fluA; (G and H) negative controls showing baseline levels of IFN-γ production by CD3– and CD3+ lymphocytes in the absence of fluA. Numbers in the dot plots refer to percentage of IFN-γ+ cells in the gated population.