Posttranscriptional regulation of II10 gene expression allows natural killer cells to express immunoregulatory function.
Natural killer (NK) cells play a well-recognized role in early pathogen containment and in shaping acquired cell-mediated immunity. However, indirect evidence in humans and experimental models has suggested that NK cells also play negative regulatory roles during chronic disease. To formally test this hypothesis, we employed a well-defined experimental model of visceral leishmaniasis. Our data demonstrated that NKp46(+)CD49b(+)CD3(-) NK cells were recruited to the spleen and into hepatic granulomas, where they inhibited host protective immunity in an interleukin-10 (IL-10)-dependent manner. Although IL-10 mRNA could be detected in activated NK cells 24 hr after infection, the inhibitory function of NK cells was only acquired later during infection, coincident with increased IL-10 mRNA stability and an enhanced capacity to secrete IL-10 protein. Our data support a growing body of literature that implicates NK cells as negative regulators of cell-mediated immunity and suggest that NK cells, like CD4(+) T helper 1 cells, may acquire immunoregulatory functions as a consequence of extensive activation.
Maroof
Asher
A
Immunology and Infection Unit, Hull York Medical School and Department of Biology, University of York, Wentworth Way, York YO10 5YW, UK.
Beattie
Lynette
L
Zubairi
Soombul
S
Svensson
Mattias
M
Stager
Simona
S
Kaye
Paul M
PM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015870:Gene Expression; D006099:Granuloma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology; D008099:Liver / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D016753:Interleukin-10