Tonsilar NK cells restrict B cell transformation by the Epstein-Barr virus via IFN-gamma.
Cells of the innate immune system act in synergy to provide a first line of defense against pathogens. Here we describe that dendritic cells (DCs), matured with viral products or mimics thereof, including Epstein-Barr virus (EBV), activated natural killer (NK) cells more efficiently than other mature DC preparations. CD56(bright)CD16(-) NK cells, which are enriched in human secondary lymphoid tissues, responded primarily to this DC activation. DCs elicited 50-fold stronger interferon-gamma (IFN-gamma) secretion from tonsilar NK cells than from peripheral blood NK cells, reaching levels that inhibited B cell transformation by EBV. In fact, 100- to 1,000-fold less tonsilar than peripheral blood NK cells were required to achieve the same protection in vitro, indicating that innate immune control of EBV by NK cells is most efficient at this primary site of EBV infection. The high IFN-gamma concentrations, produced by tonsilar NK cells, delayed latent EBV antigen expression, resulting in decreased B cell proliferation during the first week after EBV infection in vitro. These results suggest that NK cell activation by DCs can limit primary EBV infection in tonsils until adaptive immunity establishes immune control of this persistent and oncogenic human pathogen.
Strowig
Till
T
Laboratory of Viral Immunobiology, The Rockefeller University, New York, New York, United States of America.
Brilot
Fabienne
F
Arrey
Frida
F
Bougras
Gwenola
G
Thomas
Dolca
D
Muller
William A
WA
Münz
Christian
C
D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D019002:CD56 Antigen / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D014066:Palatine Tonsil / Q000166:cytology*; D017452:Receptors, IgG / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D017452:Receptors, IgG; D007371:Interferon-gamma