Development of Th17 and Treg cells during influenza viral infection in neonatal mice. (49.23)

Abstract

Abstract T cells in the neonatal lung are less activated than in adults and do not infiltrate the alveolar spaces in response to influenza virus infection. TGFβ is elevated in the lungs of neonatal mice, and since neonatal mice do not respond with a typical Th1 response, the Th17 and T regulatory (Treg) cells were evaluated. Neonatal mice had similar CD4 T cells expressing IL-17A compared to adults in the lung during viral clearance. In an adoptive transfer of adult and neonatal CD4 T cells into adult T cell receptor knockout mice (TCR-/-), neonatal T cells were able to enter the airways but failed to expand as robustly as adult T cells. In this model, neonatal CD4 T cells expressed more IL-17A than adult T cells and this coincided with increased numbers of neutrophils in the airway. Depletion studies will be used to examine the role of IL-17A and neutrophils in the clearance of influenza virus. In addition to a robust Th17 response, neonatal mice had higher levels of Tregs than adults, and these elevated levels persisted during influenza viral infection. Upon depletion of Tregs by anti-CD25 antibody, neonatal T cells still did not infiltrate into the alveolar spaces during an influenza viral infection. However, the anti-CD25 treated mice had a higher body weight and larger lymph nodes. To determine whether Tregs are responsible for the delayed viral clearance seen in neonatal mice, cytolytic T lymphocytes will be examined in neonatal mice without Tregs and plaque assays performed.