Antigen-specific CD8(+) T cells persist in the upper respiratory tract following influenza virus infection

Because little is known about lymphocyte responses in the nasal mucosa, lym phocyte accumulation in the nasal mucosa, nasal-associated lymphoid tissue (NALT), and cervical lymph nodes (CLN) were determined after primary and he terosubtypic intranasal influenza challenge of mice. T cell accumulation pe aked in the nasal mucosa on day 7, but peaked slightly earlier in the CLN ( day 5) and later (day 10) in the NALT. Tetrameric staining of nasal mucosal cells revealed a peak accumulation of CD8 T cells specific for either the H-2D(b) influenza nucleoprotein epitope 366-374 ((DNP366)-N-b) or the H-2D( b) polymerase 2 protein epitope 224-233 (D(b)PA(224)) at 7 days. By day 13, D(b)PA(224)-specific CD8 T cells were undetectable in the mucosa, whereas (DNP366)-N-b-specific CD8 T cells persisted for at least 35 days in the muc osa and spleen. After heterosubtypic virus challenge, the accumulation of C D8 T cells in the nasal mucosa was quicker, more intense, and predominantly (DNP366)-N-b specific relative to the primary inoculation. The kinetics an d specificity of the CD8 T cell response were similar to those in the CLN, but the responses in the NALT and spleen were again slower and more protrac ted. These results indicate that similar to what was reported in the lung, (DNP366)-N-b-specific CD8 T cells persist in the nasal mucosa after primary influenza infection and predominate in an intensified nasal mucosal respon se to heterosubtypic challenge. In addition, differences in the kinetics of the CD8 T cell responses in the CLN, NALT, and spleen suggest different ro les of these lymphoid tissues in the mucosal response.