Understanding how immunological memory is maintained in peripheral tissues such as the lung is pivotal for designing a vaccine against the tissue-specific infection of influenza A. Despite much progress towards understanding how CD8 T cells participate in immune responses against influenza, long-term protection has been difficult to achieve. This is in part due to the decline in number of competent effector memory cells in the lung airways, the portal of viral entry, despite continued recruitment of a secondary pool of memory cells to the lung. The goal of this proposal is to generate an understanding how we can both recruit and sustain migrants in the lung airways to prevent future influenza infections.
In Aim 1 we will determine the source of memory cells which seed the lung airways at late time points following infection using both an adoptive transfer system and genetic and surgical manipulation to selectively add or remove populations of memory cells.
In Aim 2 we will determine how IL-15 influences the migration and homeostatic proliferation of influenza- specific memory cells in the lung. These studies will place a special emphasis on the interaction between memory cells and lung-specific epithelial and endothelial cells. Whether these cells provide signals, such as IL-15, to induce both trafficking and homestatic proliferation will be explored. Together, these studies will assist in identification of and recruitment of cells which maintain long-term protective CD8 T cell immunity in the lung and will help in the development of vaccines. ? ? ?
| Verbist, Katherine C; Klonowski, Kimberly D (2012) Functions of IL-15 in anti-viral immunity: multiplicity and variety. Cytokine 59:467-78 |
| Verbist, Katherine C; Rose, David L; Cole, Charles J et al. (2012) IL-15 participates in the respiratory innate immune response to influenza virus infection. PLoS One 7:e37539 |
| Verbist, Katherine C; Field, Mary B; Klonowski, Kimberly D (2011) Cutting edge: IL-15-independent maintenance of mucosally generated memory CD8 T cells. J Immunol 186:6667-71 |
| Verbist, Katherine C; Cole, Charles J; Field, Mary B et al. (2011) A role for IL-15 in the migration of effector CD8 T cells to the lung airways following influenza infection. J Immunol 186:174-82 |
