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

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 (T) 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 T 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 T cells are under development, with the hope to induce stable and highly reactive lung T cells through mucosal administration or "prime-and-pull" strategy. In this review, we will summarize recent advances in lung T 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.