MECHANISMS OF LUNG SURVEILLANCE BY PATHOGEN-SPECIFIC CYTOTOXIC T LYMPHOCYTES

Cytotoxic T lymphocyte (CTL)-mediated immunity plays a critical role in clearance of influenza virus-infected cells through contact-dependent interactions. Recent studies have described stationary tissue-resident memory (Trm) T cells which maintain CD69 and CD103 expression in peripheral tissues after local infections. These Trm cells are believed to contribute to protection after local reinfection, because they stay near the site of inoculation. Parabiosis studies previously showed that some non-migratory virus-specific CD8 T cells expressed both CD69 and CD103 in the airways after influenza virus infection. Since the TGFβ and TcR signaling pathways induce CD103 and CD69 expression on CD8 T cells in other models, I hypothesized that environmental factors and residual viral products support sustained surveillance of the lungs by pathogen-specific CTLs. In chapter 3, I used mice that express a dominant negative form of the TGFβRII (dnTGFβRII) to investigate the role of TGFβ signals in regulation of virus-specific CTL responses in the lungs after influenza virus infection. My dat