Latent herpesvirus infection arms NK cells.
Natural killer (NK) cells were identified by their ability to kill target cells without previous sensitization. However, without an antecedent "arming" event, NK cells can recognize, but are not equipped to kill, target cells. How NK cells become armed in vivo in healthy hosts is unclear. Because latent herpesviruses are highly prevalent and alter multiple aspects of host immunity, we hypothesized that latent herpesvirus infection would arm NK cells. Here we show that NK cells from mice latently infected with Murid herpesvirus 4 (MuHV-4) were armed as evidenced by increased granzyme B protein expression, cytotoxicity, and interferon-gamma production. NK-cell arming occurred rapidly in the latently infected host and did not require acute viral infection. Furthermore, NK cells armed by latent infection protected the host against a lethal lymphoma challenge. Thus, the immune environment created by latent herpesvirus infection provides a mechanism whereby host NK-cell function is enhanced in vivo.
Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Douglas W
DW
White
Catherine R
CR
Keppel
Stephanie E
SE
Schneider
Tiffany A
TA
Reese
James
J
Coder
Jacqueline E
JE
Payton
Timothy J
TJ
Ley
Herbert W
HW
Virgin
Todd A
TA
Fehniger
D000818:Animals; D015550:Cell Degranulation / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D016654:Genes, RAG-1; D053804:Granzymes / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018144:Rhadinovirus; D014412:Tumor Virus Infections / Q000276:immunology*
D007371:Interferon-gamma; D053804:Granzymes