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J Louise Lines, Melissa Hollifield, Linda Cauley, Beth Garvy, The T Cell Response to Influenza in Neonates (43.29), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Page S42, https://doi.org/10.4049/jimmunol.178.Supp.43.29
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Abstract
Influenza is a significant cause of mortality and morbidity in children. However, very little data exists on the neonatal immune response to influenza. We have found that neonatal mice are highly vulnerable to influenza and only control much reduced doses of virus.
In this study, the T cell response to intranasal influenza infection was compared between mice infected as adults or at 2 days old. In neonates, despite significant expansion of T cells in draining lymph nodes, entry of T cells into the lungs was defective. In adults, high numbers of CD4 and CD8 T cells peaked in the lung interstitium and alveolar spaces by 10 days post infection. However, in neonates, CD8 T cells entered the lungs by day 10 post-infection, but not to high levels, while CD4 T cell entry was delayed until 3 weeks of age. Interestingly, while CD4 T cells reached adult levels in the interstitia, they were unable to cross the epithelial barrier into the alveoli. The delayed entry of CD4 T cells corresponded with a delay in TNFα production and a lack of IFNγ which may consequently lead to delayed upregulation of adhesion molecules and chemokines.
Despite the poor response to influenza as neonates, mice infected at 2 days old with the PR8 strain of influenza did develop T cell memory. Mice were protected when subsequently infected as adults with a lethal dose of HKx31, a strain that shares only the internal T cell antigens with PR8. These data suggest that the acute sensitivity of neonates to influenza may be a consequence of defective T cell migration.
