Legend of the Sentinels: Development of Lung Resident Memory T Cells and Their Roles in Diseases

Abstract

SARS-CoV-2 is wreaking havoc around the world. To get the world back on track, hundreds of vaccines are under development. A deeper understanding of how the immune system responds to SARS-CoV-2 re-infection will certainly help. Studies have highlighted various aspects of T cell response in resolving acute infection and preventing re-infections. Lung resident memory T (TRM) cells are sentinels in the secondary immune response. They are mostly differentiated from effector T cells, construct specific niches and stay permanently in lung tissues. If the infection recurs, locally activated lung TRM cells can elicit rapid immune response against invading pathogens. In addition, they can significantly limit tumor growth or lead to pathologic immune responses. Vaccines targeting TRM cells are under development, with the hope to induce stable and highly reactive lung TRM cells through mucosal administration or “prime-and-pull” strategy. In this review, we will summarize recent advances in lung TRM cell generation and maintenance, explore their roles in different diseases and discuss how these cells may guide the development of future vaccines targeting infectious disease, cancer, and pathologic immune response.

SARS-CoV-2 spike-FLIPr fusion protein plus lipidated FLIPr protects against various SARS-CoV-2 variants in hamsters

“…SARS-CoV-2 continues to mutate, changing its surface antigens to escape antibody-mediated neutralization ( 7 ). Thus, memory T cells, in particular lung T RM , are thought to be another crucial immunity in providing effective protection against the spread of viruses and the development of severe diseases ( 70 – 73 ). In this study, mixing the antigen with rLF can increase IFN-γ producing CD4 + and CD8 + T RM in the lung ( Fig.…”

Comprehensive immune landscape of lung-resident memory CD8+ T cells after influenza infection and reinfection in a mouse model

“…It has been revealed that circulating memory CD8 + T cells can be recruited into the lung and converted into Trm phenotype without antigen recognition (Van Braeckel-Budimir and Harty, 2017 ). Airway T cells are mainly replenished by recruitment from the lung interstitium (Ely et al, 2006 ), and Trm cells in the interstitium receive continuous compensation from circulating Tem cells (Qian et al, 2020 ). However, several studies mentioned that the lung Trm compartment was not replaced by the circulating memory pool (Takamura et al, 2016 ; Van Braeckel-Budimir and Harty, 2017 ).…”

Tissue-resident immunity in the lung: a first-line defense at the environmental interface

“…T RM and B RM cells are also implicated in the pathogenesis of asthma [73,262]. Specifically, Th2-T RM cells secrete cytokines that promote and sustain airway eosinophilia [72] [262].…”

“…T RM and B RM cells are also implicated in the pathogenesis of asthma [73,262]. Specifically, Th2-T RM cells secrete cytokines that promote and sustain airway eosinophilia [72] [262]. Upon HDM exposure, IL-2 signalling enables the generation, migration and retention of allergen-specific Th2-T RM cells in the lungs, where they drive AAI [72].…”