In situ imaging unveiled location of protective endogenous CD8 T cell response in lung (MUC1P.916)

Abstract

Abstract The anatomic distribution of protective endogenous memory CD8 T cell response in the lung—a common site of pathogen invasion—is poorly understood. We report that endogenous CD8 T cell memory installed by local pulmonary, but not systemic, vaccination resulted in faster viral control and enhanced protection to a lethal respiratory viral challenge in mice. Enhanced protection depended on elicitation of a distinct CXCR3LO resident CD8 T cell memory population (CD8 TRM) confined to the pulmonary interstitium. CD8 TRM sensed the pathogen and rapidly initiated a local immune response before inflammation-induced recruitment of lung vascular and/or circulating memory CD8 cells. Imaging of protective CD8 T cell response in lungs by exploiting in situ staining with fluorescent MHC class I tetramers coupled with Sheet Plane Illumination Microscopy (SPIM) platform uncovered that CD8 TRM are retained within immunologically correct locations, which include the delicate alveoli walls outside of the alveolar capillary network - the most vulnerable sites affected by lower airway infection. Such a location of memory CD8 T cell response may allow prompt surveillance of infected alveolar epithelium without need for the egress into the alveolar space. In sum, our study unveiled novel dimensional information of memory T cell response that localize to those anatomic sites of the lung that are critical for host defense.