Recruitment of memory CD8+ T cells to the lung airways

Trudeau Institute, Inc., Saranac Lake NY

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): Respiratory viruses are a major cause of morbidity and mortality worldwide. Memory CD8+ T cells, established after primary infection or vaccination, confer protection against a secondary virus challenge through the rapid accumulation of antigen-specific cells in the lung tissue and lung airways. Elucidation of the factors governing the recruitment memory T cells to the lung airways is of great importance for the design of future vaccines designed to promote cellular immunity. In the present proposal, we will take advantage of the well-established model of respiratory virus infection (Sendai virus) to investigate the recruitment of memory CD8 T cells to the lung airways in response to inflammation. Interestingly, despite numerous studies investigating the recruitment of effector T cells the lungs, there is very little published data regarding the recruitment of established memory T cells. Preliminary data show that different toll-like receptor (TLR) ligands can induce recruitment of memory T cells into the lung airways. However, the mechanisms governing recruitment to the lung airways under steady-state and inflammatory conditions are not known. The underlying hypothesis of the proposal is that TLR ligands induce the expression of a set of chemokines that are required for the recruitment of memory CD8 T cells to the lung airways. This hypothesis will be tested by (i) characterizing the expression of chemokines following TLR ligand stimulation and determining the relevance of these chemokines for recruitment to the lung airways, and (ii) determining the ability of TLR ligands to boost protective immunity in vaccinated mice through the recruitment of memory CD8 T cells to the lung airways. Relevance of research to public health: Current vaccines against respiratory viruses such as influenza are inadequate in that they provide only seasonal protection against specific strains of the virus. A cellular- based vaccine, directed against the unchanging internal components of the virus, would confer broad protection against a range of influenza strains, thereby minimizing the need for repeated vaccinations and simplifying vaccine production. The current proposal will investigate the mechanisms by which memory T cells are recruited to the site of respiratory virus infection, which has important implications for the design of future cellular-based vaccines. [unreadable] [unreadable] [unreadable]