The Limits in Infant Immunity

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Science  24 Aug 2012:
Vol. 337, Issue 6097, pp. 891
DOI: 10.1126/science.337.6097.891-b

Natural killer (NK) cells control viral infections swiftly, releasing lytic factors that destroy infected cells shortly after infection. But infants and neonates are susceptible to viral infections in part because they lack the mature form of these powerful immune cells. Marcoe et al. have discovered a factor that limits this arsenal early in life. The authors found that during mouse infancy, transforming growth factor–β (TGF-β) blocks a terminal step in NK cell maturation. TGF-β blocked the generation of mature NK cells from mouse stem cell precursors in vitro. In mice that were genetically engineered to lack a functional receptor for TGF-β in NK cells, the number of mature NK cells present at 10 days of age was equivalent to that in 56-day-old normal mice. In addition to faster maturation, infant mice lacking NK cell TGF-β receptor signaling were resistant to viral infection. Analysis of mRNA points to genes that control the cell division cycle—p21 and Cdc7—as targets of TGF-β, arresting the production of NK cells as they mature. The expression of transcription factors that push NK cells through the final stage of maturation is also limited by TGF-β. The findings raise the possibility that inactivating TGF-β signaling could prevent the deficit of NK cells during infancy.

Nat. Immunol. 11, 10.1038/ni.2388 (2012).

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