T cell-dependent production of IFN-gamma by NK cells in response to influenza A virus.
The role of human NK cells in viral infections is poorly understood. We used a cytokine flow-cytometry assay to simultaneously investigate the IFN-gamma response of NK and T lymphocytes to influenza A virus (fluA). When PBMCs from fluA-immune adult donors were incubated with fluA, IFN-gamma was produced by both CD56(dim) and CD56(bright) subsets of NK cells, as well as by fluA-specific T cells. Purified NK cells did not produce IFN-gamma in response to fluA, while depletion of T lymphocytes reduced to background levels the fluA-induced IFN-gamma production by NK cells, which indicates that T cells are required for the IFN-gamma response of NK cells. The fluA-induced IFN-gamma production of NK cells was suppressed by anti-IL-2 Ab, while recombinant IL-2 replaced the helper function of T cells for IFN-gamma production by NK cells. This indicates that IL-2 produced by fluA-specific T cells is involved in the T cell-dependent IFN-gamma 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.
He
Xiao-Song
XS
Department of Medicine, Stanford University of School of Medicine, Stanford, California, USA. xiaosong@stanford.edu
Draghi
Monia
M
Mahmood
Kutubuddin
K
Holmes
Tyson H
TH
Kemble
George W
GW
Dekker
Cornelia L
CL
Arvin
Ann M
AM
Parham
Peter
P
Greenberg
Harry B
HB
D000328:Adult; D000368:Aged; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D017252:CD3 Complex / Q000096:biosynthesis / Q000378:metabolism; D019002:CD56 Antigen / Q000096:biosynthesis; D002460:Cell Line; D004285:Dogs; D005434:Flow Cytometry; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D007376:Interleukin-2 / Q000737:chemistry / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008875:Middle Aged; D009975:Orthomyxoviridae / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D017252:CD3 Complex; D019002:CD56 Antigen; D007376:Interleukin-2; D011994:Recombinant Proteins; D020126:Brefeldin A; D007371:Interferon-gamma