Antigen-specific and non-specific CD4+ T cell recruitment and proliferation during influenza infection

To track epitope-specific CD4+ T cells at a single-cell level during influenza infection, the MHC class II-restricted OVA323-339 epitope was engineered into the neuraminidase stalk of influenza/A/WSN, creating a surrogate viral antigen. The recombinant virus, influenza A/WSN/OVAII, replicated well, was cleared normally, and stimulated both wild-type and DO11.10 or OT-II TCR transgenic OVA-specific CD4+ T cells. OVA-specific CD4 T cells proliferated during infection only when the OVA epitope was present. However, previously primed (but not naive) transgenic CD4+ T cells were recruited to the infected lung both in the presence and absence of the OVA323-339 epitope. These data show that, when primed, CD4+ T cells may traffic to the lung in the absence of antigen, but do not proliferate. These results also document a useful tool for the study of CD4 T cells in influenza infection.