Editors' ChoiceImmunology

Education isn’t everything (for infant immunity)

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Science Translational Medicine  20 Sep 2017:
Vol. 9, Issue 408, eaao6128
DOI: 10.1126/scitranslmed.aao6128


A deficit in tissue-resident memory T cell production helps explain virus susceptibility in early life.

As any new parent can attest, infants get frequent viral infections. The usual explanation is that the adaptive immune system of infants needs to be honed by pathogen exposure to become fully effective. However, Zens et al. recently discovered an infant vulnerability to viruses that is unrelated to immune education.

Using a mouse model of influenza infection, the authors found that infant mice have trouble establishing lung tissue–resident memory T (TRM) cells. TRMs are forward-deployed lymphocytes that are stationed in the lung and other barrier organs after an acute infection and speed up pathogen clearance in the event of repeat exposure. Because infant mice cannot generate TRMs effectively, their response to repeat influenza infection was highly dependent on circulating T cells. As a result, when circulating T cells were experimentally depleted in these young animals, they became severely ill upon reinfection. In contrast, mice infected initially as adults and that had sufficient numbers of TRMs developed only mild disease even with depletion of their circulating T cells. Another consequence of defective TRM production in infant mice was reduced protective immunity after receiving live attenuated influenza vaccine. The authors compared gene expression in adult and infant T cells and noted that infant cells have increased activity of T-bet, a master regulator of T cell differentiation in mice and humans. Crucially, reducing T-bet expression in infant mice stimulated lung TRM development after an initial influenza infection and improved immune responses upon repeat exposure.

Why infant T cells should be biased away from becoming TRMs when they are so clearly beneficial to adult immunity is unknown. The authors speculate that excess T-bet activity in infants could have the benefit of elevating interferon-γ production and thereby supercharge innate immunity in early life. If so the results of Zens et al. are notable because they illustrate the trade-offs that go into building an immune system that must serve an organism through all the changes in body composition and circumstance that occur as it grows. Given the increasing complexity of immunotherapies currently in development, understanding these trade-offs will be important to maximize future medical gains.

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