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Supplemental oxygen administered to preterm infants is an important clinical intervention, but it is associated with life-long changes in lung development and increased sensitivity to respiratory viral infections. The precise immunological changes caused by neonatal oxygen treatment remain poorly understood. We previously reported that adult mice exposed to supplemental oxygen as neonates display persistent pulmonary inflammation and enhanced mortality after a sublethal influenza A virus infection. These changes suggest that neonatal hyperoxia impairs the cytotoxic CD8+ T cell response required to clear the virus. In this study, we show that although host resistance to several different strains of influenza A virus is reduced by neonatal hyperoxia, this treatment does not impair viral clearance, nor does it alter the magnitude of the virus-specific CD8+ T cell response to primary infection. Moreover, memory T cells are sufficient to ameliorate the increased morbidity and mortality and alleviate the excessive lung damage observed in mice exposed to high oxygen levels as neonates, and we attribute this sufficiency principally to virus-specific memory CD8+ T cells. Thus, we show that neonatal hyperoxia reduces host resistance to influenza virus infection without diminishing the function of cytotoxic T lymphocytes or the generation of virus-specific memory T cells and that CD8+ memory T cells are sufficient to provide protection from negative consequences of this important life-saving intervention. Our findings suggest that vaccines that generate robust T cell memory may be efficacious at reducing the increased sensitivity to respiratory viral infections in people born prematurely.

clinical and vaccine immunology

Memory CD8 <sup>+</sup> T Cells Are Sufficient To Alleviate Impaired Host Resistance to Influenza A Virus Infection Caused by Neonatal Oxygen Supplementation

Memory CD8 + T Cells Are Sufficient To Alleviate Impaired Host Resistance to Influenza A Virus Infection Caused by Neonatal Oxygen Supplementation

Memory CD8 ⁺ T Cells Are Sufficient To Alleviate Impaired Host Resistance to Influenza A Virus Infection Caused by Neonatal Oxygen Supplementation