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. 2016 Dec 12;213(13):2897–2911. doi: 10.1084/jem.20160167

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© 2016 Abboud et al.

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Figure 6. — Memory CD8 T cell subsets form tissue-specific layered defense to protect against lethal respiratory virus infection. Airway epithelial cells serve as the primary location for virus-replication and spread after respiratory virus infection. (A) CD27^hiCXCR3^hi memory CD8 T cells mobilize from the circulation into the lung parenchyma and airway epithelial foci cell and function as the first line of defense against pathogen exposure. (B) If mobile-infected cells successfully breach this first line of defense, the host possesses a second layer of protection, the CD27^loCXCR3^lo memory subsets, which are generated directly from CD27^hiCXCR3^hi in situ in response to pathogen-specific inflammatory co-signals. Here, the immune system adapts its response to engage and kill infected cells to prevent systemic viral dissemination and eventual death. (C) CD27^loCXCR3^lo cannot mobilize to the epithelial foci and are eventually overwhelmed by the invading virus. The concept of layered immunity allows the adaptive immune system a certain level of plasticity to mount faster and stronger attacks each time the virus is encountered.