Type I interferons regulate cytolytic activity of memory CD8⁺ T cells in the lung airways during respiratory virus challenge

Kohlmeier JE, et al. Immunity. 2010; 33: 96-105.

Speaker: Te-Hsin Yen (顏德欣)                                             Time: 15:10~16:00, Mar 30, 2011

Commentator: Dr. Ching-Chuan Liu (劉清泉 老師)           Place: Room 601

Abstract:

During a viral infection, the immune system not only makes a rapid pathogen-specific response at these sites to destroy the invading pathogen, but also generates long-lived memory T cells that localized to peripheral tissues for many months. However, lung airway-resident memory T cells in resting mice are poorly cytolytic compared to effector T cells and this decreased lytic activity correlated with reduced granzyme protein¹. In this study, the authors demonstrated memory CD8⁺ T cells recruited to the airways are primed to enhance lytic activity after an unrelated virus infection in Sendai-immune mice. Further, they analysed granzyme B (gzmB) protein is important for the lytic activity of memory CD8⁺ T cells in the airways through an antigen-independent stimulation. Interestingly, gzmB protein expression and memory T cells lytic activity is limited to cells recently recruited to the airways. STAT1 is required for signaling through several cytokine receptors associated with inflammatory responses. In Stat1^-/- mice, they found STAT1 signaling is required for the antigen-independent expression of gzmB protein in memory CD8⁺ T cells. Type I IFNs, IFN-g, and IL-27 bind to their receptors that require STAT1 for signal transduction². They generated the cytokine receptor-deficient chimeras mice and infected them with Sendai virus. After challenging an unrelated virus, they found the signaling through Ifnar1 is required for antigen-independent expression of gzmB protein and lytic activity of memory T cells in the lung airways. Finally, they assessed the importance of Ifnar1 signaling for expression of gzmB protein in memory CD8⁺ T cells when secondary infection by using complete chimeras mice which reconstituted with WT orIfnar1^-/- bone marrow (BM). The Ifnar1^-/- BM mice showed a significantly decreased ability to control viral loads. Together, the paper demonstrated type I interferon is a key for rapid upregulation of effector function within circulating memory CD8⁺ T cells, ensuring efficient control of infection.

References:

1.          Vallbracht, S., Unso¨ ld, H., and Ehl, S. Functional impairment of cytotoxic T cells in the lung airways following respiratory virus infections. Eur. J. Immunol. 2006; 36: 1434–1442.

2.          Durbin, J.E., Hackenmiller, R., Simon, M.C., and Levy, D.E. Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease. Cell. 1996; 84: 443–450.