The mechanism of protection against influenza by transfer of Tc17, an IL-17 secreting CD8 T cell subset. (46.5)

Abstract

Abstract Interleukin (IL) -17 secreting CD4 T (Th)17 and CD8 T (Tc)17 effector cells are found in the lung following primary challenge with influenza A and blocking antibody to IL-17 increases weight loss and reduces survival. Tc17 effectors can be generated in vitro using naïve CD8 T cells from OT-1 T cell receptor (TcR) transgenic mice. T cell numbers expand 20 fold and a majority secretes IL-17, but little IFN-γ. Tc17 effectors are negative for granzyme B, for perforin message and lack cytolytic activity in vitro, in contrast to Tc1 effectors. Many of the Tc17 effectors become IFN-γ/IL-17 double producers after adoptive transfer and kill targets by a Fas dependent, perforin independent, pathway in an in vivo CTL assay. Adoptively transferred Tc17 cells expand greatly after transfer to naïve recipients following challenge and can protect them against lethal influenza infection. Transfer of Tc17 effector cell enhances the infiltration of neutrophils and monocytes to lung after influenza infection and protects against the development of respiratory distress much more effectively than transfer of equivalent numbers of Tc1 effectors. Additional mechansims of protection are being explored. This work was supported by NIH AI046530 and the Trudeau Institute.