Persistence in Temporary Lung Niches: A Survival Strategy of Lung-Resident Memory CD8⁺T Cells

Abstract

Respiratory virus infections, such as those mediated by influenza virus, parainfluenza virus, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus (SARS-CoV), rhinovirus, and adenovirus, are responsible for substantial morbidity and mortality, especially in children and older adults. Furthermore, the potential emergence of highly pathogenic strains of influenza virus poses a significant public health threat. Thus, the development of vaccines capable of eliciting long-lasting protective immunity to those pathogens is a major public health priority. CD8+ Tissue-resident memory T (TRM) cells are a newly defined population that resides permanently in the nonlymphoid tissues including the lung. These cells are capable of providing local protection immediately after infection, thereby promoting rapid host recovery. Recent studies have offered new insights into the anatomical niches that harbor lung CD8+ TRM cells, and also identified the requirement and limitations of TRM maintenance. However, it remains controversial whether lung CD8+ TRM cells are continuously replenished by new cells from the circulation or permanently lodged in this site. A better understanding of how lung CD8+ TRM cells are generated and maintained and the tissue-specific factors that drive local TRM formation is required for optimal vaccine development. This review focuses on recent advance in our understanding of CD8+ TRM cell establishment and maintenance in the lung, and describes how those processes are uniquely regulated in this tissue.

A single intranasal dose of chimpanzee adenovirus-vectored vaccine confers sterilizing immunity against SARS-CoV-2 infection

“…Re-stimulation ex vivo with a pool of S peptides resulted in a marked increase in IFNg and granzyme B producing CD8 + T cells in the lungs of mice that received the ChAd-SARS-CoV-2-S vaccine (Fig 4H). Specifically, a population of IFNg-secreting, antigen-specific CD103 + CD69 + CD8 + T cells in the lung was identified ( Fig 4I) which is phenotypically consistent with vaccine-induced resident memory T cells (Takamura, 2017). In the spleen, we detected antibody-secreting plasma cells producing IgA or IgG against the S protein after intranasal immunization with ChAd-SARS-CoV-2-S ( Fig 4J).…”

Tissue-resident lymphocytes: from adaptive to innate immunity

“…31 In addition, populations of CD69 + CD103 + CXCR6 + T RM cells expressing low levels of sphingosine-1-phosphate receptor 1 (S1PR1) and KLF2, and CD69 + CD103 + CXCR6 + CXCR3 + T RM cells with a Tbet lo Eomes lo Blimp-1 hi Hobit lo phenotype have been identified in the liver. 32,33 CD103 + T RM cells are often present in the sensory ganglia, 11 skin, 11,13,15,16,34 lungs, 15,[35][36][37] salivary gland, 16,17,38 reproductive tract, 17,39 thymus 40 and pancreas, 17,41 and a minimal number of CD103 + T RM cells can also be found in the heart. 17 Of note, intravascular staining has enabled the discovery that 95% of CD69 + CD103 + T RM cells isolated from the mouse lung via standard methods are confined to the pulmonary vasculature instead of the lung tissue, suggesting an overestimate of the T RM population within the lung.…”

Immunity to Influenza Infection in Humans

“…Two possible non-mutually exclusive possibilities can be envisioned. Cytotoxic CD4 T cells may serve as a complementary mechanism, eliminating infected cells at selected sites within the lung, perhaps controlled by a unique array of lung positioning molecules (Richter et al 2007;Takamura 2017). Recent studies have revealed the diversity of infected and antigen-bearing cells detectable in the lung early after infection (DiPiazza et al 2017) that may be located at distinct sites in the respiratory tract.…”