Changes in Natural Killer Cells in Aged Mice
Immune dysfunctions in the elderly result in increased susceptibility to infectious diseases, cancer, or autoimmune diseases. Natural killer (NK) cells are bone marrow derived lymphocytes crucial for host defense against several infections and cancer. It is known that aged C57BL/6 mice compared to young mice have decreased numbers of mature NK cells in the blood, spleen, and bone marrow, resulting in susceptibility to mousepox, a lethal disease caused by Ectromelia virus. The chapter discusses newly described age-related defects in NK cells including reduced proliferation in vivo, dysregulated expression of activating and inhibitory receptors, and altered expression of collagen binding integrins. The chapter also describes that the defect in NK maturation is the consequence of deficient maturational cues provided by bone marrow stromal cells. Treatment with complexes of the cytokine IL-15 and IL-15Rα induce massive expansion of the NK cells but most of these NK cells remain immature and are unable to restore resistance to mousepox. Therefore, it may be crucial to design therapies that specifically increase mature NK cell numbers in the aged.
KeywordsAging Natural killer cells Immunosenescence Cellular immunology Immune cell development Mice NK cell development and maturation Bone marrow Stromal cell defect Integrins
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