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Proliferation cues 'natural killer' cells for job change
Date:6/12/2014

but it does come up in some pretty important ones. Scientists have observed it in human cases of hepatitis C, for example.

In the new study, the researchers used a different virus, known as MCMV in mice, as part of their investigation of NK proliferation. The human version, CMV, can cause birth defects if it's active in a woman who is pregnant.

The first step was to confirm that in mice infected with MCMV, NK cells were indeed pumping out the IL-10. The researchers noticed that in highly infected mice, NK cells produced IL-10 about 3.5 days into the infection days later than when they'd produce IFN-gamma, a protein that helps to mount, rather than defuse, the immune system response.

In lab cultures, they found that only cells that were about 3.5 days post infection would produce IL-10. A subsequent experiment showed that exposure to a virus wasn't necessary, per se, but several rounds of replication and proliferation (over about 3 days) enabled the IL-10 production.

"Taken together, these studies show that the NK cell IL-10 response is associated with extensive proliferation, either under in vitro conditions independent of infection, or in vivo during infection," wrote the authors, including co-lead author and former Brown postdoctoral researcher Seung-Hwan Lee, who is now at the University of Ottawa.

Having shown that IL-10 production was associated with NK cell proliferation, Tarrio, Biron and colleagues sought even more evidence: The mechanism in the NK cells that triggers the switch to IL-10 production.

They found it by comparing the genome-wide conformation of DNA in NK cells before and after proliferation in infected mice. They found that in NK cells that hadn't undergone the proliferation process, the gene for IL-10 was tightly wrapped up and inaccessible for expression. Post-proliferation cells had IL-10 genes that were more open and access
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Contact: David Orenstein
david_orenstein@brown.edu
401-863-1862
Brown University
Source:Eurekalert  

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