Tissue-specific programming of memory CD8 T cell subsets impacts protection against lethal respiratory virus infection
0303 health sciences
Mice, Transgenic
CD8-Positive T-Lymphocytes
Respirovirus Infections
Respirovirus
3. Good health
Pulmonary Alveoli
Mice
03 medical and health sciences
Animals
Female
Immunologic Memory
Respiratory Tract Infections
Research Articles
DOI:
10.1084/jem.20160167
Publication Date:
2016-11-22T16:16:24Z
AUTHORS (7)
ABSTRACT
How tissue-specific anatomical distribution and phenotypic specialization are linked to protective efficacy of memory T cells against reinfection is unclear. Here, we show that lung environmental cues program recently recruited central-like memory cells with migratory potentials for their tissue-specific functions during lethal respiratory virus infection. After entering the lung, some central-like cells retain their original CD27hiCXCR3hi phenotype, enabling them to localize near the infected bronchiolar epithelium and airway lumen to function as the first line of defense against pathogen encounter. Others, in response to local cytokine triggers, undergo a secondary program of differentiation that leads to the loss of CXCR3, migration arrest, and clustering within peribronchoarterial areas and in interalveolar septa. Here, the immune system adapts its response to prevent systemic viral dissemination and mortality. These results reveal the striking and unexpected spatial organization of central- versus effector-like memory cells within the lung and how cooperation between these two subsets contributes to host defense.
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