Airway-Resident Memory CD8 T Cells Provide Antigen-Specific Protection against Respiratory Virus Challenge through Rapid IFN-γ Production

Abstract

Airway resident memory CD8 T (TRM) cells are a distinctive TRM population with a high turnover rate and a unique phenotype influenced by their localization within the airways. Their role in mediating protective immunity to respiratory pathogens, while suggested by many studies, has not been directly proven. This study provides definitive evidence that airway CD8 TRM cells are sufficient to mediate protection against respiratory virus challenge. Despite being poorly cytolytic in vivo and failing to expand after encountering antigen, airway CD8 TRM cells rapidly express effector cytokines, with IFN-γ being produced most robustly. Notably, established airway CD8 TRM cells possess the ability to produce IFN-γ faster than systemic effector memory CD8 T cells. Furthermore, naïve mice receiving intratracheal transfer of airway CD8 TRM cells lacking the ability to produce IFN-γ were less effective at controlling pathogen load upon heterologous challenge. This direct evidence of airway CD8 TRM cell-mediated protection demonstrates the importance of these cells as a first line of defense for optimal immunity against respiratory pathogens and suggests they should be considered in the development of future cell-mediated vaccines.

A Distinct Lung-Interstitium-Resident Memory CD8 + T Cell Subset Confers Enhanced Protection to Lower Respiratory Tract Infection

“…Accordingly, IN infection with live influenza virus elicited a robust T rm that localized mostly around the large airways and blood vessels of the lungs (Wu et al, 2014). Other studies have suggested a protective role for CXCR3 HI memory CD8 + T cells, also induced by viral infection, but were located within the airway lumen (McMaster et al, 2015; Slutter et al, 2013). Our findings extend the types of protective T rm that patrol the lungs.…”

Tissue Distribution of Memory T and B Cells in Rhesus Monkeys following Influenza A Infection

“…It has been suggested that the ability of memory T cells to home to the lung parenchyma as T RM is critical to control lung pathogens such as influenza and Mycobacterium tuberculosis (15,16 (53). In this study, we did not compare the kinetics of cytokine production between lung CD103 + CD8…”

Tissue-Specific Control of Tissue-Resident Memory T Cells

“…Further, cooperative action from both CXCR3 hi and CXCR3 lo lung T RM s is required for the protection against lethal respiratory VACV challenge 12. Considering that CXCR3 hi airway-resident CD8 + T cells are established protectors against respiratory infections, 82,83 lung T RM cells may not represent a homogenous population of cells. Instead, different subsets or differentiation stages of T RM cells may occupy different niches and cooperate to achieve maximal protection.…”