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Fang M , Roscoe F , Sigal LJ
Age-dependent susceptibility to a viral disease due to decreased natural killer cell numbers and trafficking
J Exp Med. 2010 Oct 25;207(11) :2369-81
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Although it is well known that aged hosts are generally more susceptible to viral diseases than the young, specific dysfunctions of the immune system directly responsible for this increased susceptibility have yet to be identified. We show that mice genetically resistant to mousepox (the mouse parallel of human smallpox) lose resistance at mid-age. Surprisingly, this loss of resistance is not a result of intrinsically defective T cell responses. Instead, the primary reason for the loss of resistance results from a decreased number of total and mature natural killer (NK) cells in the blood and an intrinsic impairment in their ability to migrate to the lymph node draining the site of infection, which is essential to curb systemic virus spread. Hence, our work links the age-dependent increase in susceptibility to a viral disease to a specific defect of NK cells, opening the possibility of exploring treatments to improve NK cell function in the aged with the goal of enhancing their resistance to viral diseases.
Fang, Min Roscoe, Felicia Sigal, Luis J CA006927/CA/NCI NIH HHS/United States R01AI065544/AI/NIAID NIH HHS/United States R21AI077021/AI/NIAID NIH HHS/United States Research Support, N.I.H., Extramural United States The Journal of experimental medicine J Exp Med. 2010 Oct 25;207(11):2369-81. Epub 2010 Sep 27.