Neuraminidase-mediated TGF-β activation facilitates evolution of protective Th17 immunity

Autor: Avijit Dutta, Ching-Tai Huang, Tse-Ching Chen, Chun-Yen Lin, Yung-Chang Lin, Chia-Shiang Chang, Yueh-Chia He, Yu-Lin Huang
Rok vydání: 2017
Předmět:
Zdroj: The Journal of Immunology. 198:78.22-78.22
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.198.supp.78.22
Popis: The immune system responds to influenza virus infection for eradication of the virus but the associated inflammation may cause tissue damage to the host. In our antigen-specific mouse system, naïve influenza hemagglutinin (HA)-specific CD4+ T cells adoptively transferred with infection respond with Th1 phenotype and produce IFN-γ. Some of them secrete IL-17 as well. Second batch HA specific CD4+ T cells, adoptively transferred on day 4 after infection and the first transfer, respond to the infection with Th17 phenotype. They produce IL-17 but not IFN-γ. Both the Th1 and Th17 cells are activated with similar levels of ZAP-70 phosphorylation and T-bet induction. For the Th17 cells, IFN-γ deficiency is associated with excessive ROR-γt induction and altered T-bet dominance. Th17 cells display surface LAG-3 expression, suppress T cell activation in vitro and decrease lung inflammation in vivo. The evolution of Th17 cells is augmented in IL-10 deficiency, with IL-10 knockout mice as the recipients transferred with IL-10 knockout HA specific CD4+ T cells. There is increased neuraminidase-mediated TGF-β activation in this IL-10 deficient environment. Viral neuraminidase mediated TGF-β activation in the first batch of HA specific CD4+ T cells facilitates the Th17 evolution of the 2nd batch of cells. The 6.5 T cell receptor (TCR) transgenic mice of monotonous HA specific TCR repertoire respond to influenza virus infection with Th17 deviation and demonstrate survival benefit. Consecutive waves of naïve HA specific T cells from the thymus in 6.5 mice may evolve with mechanisms similar to consecutive adoptive transfers. Evolution of protective Th17 immunity is facilitated by neuraminidase-mediated TGF-β activation.
Databáze: OpenAIRE
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