Every Breath You Take: The Impact of Environment on Resident Memory CD8 T Cells in the Lung

Abstract

Resident memory T cells (TRM) are broadly defined as a population of T cells, which persist in non-lymphoid sites long-term, do not re-enter the circulation, and are distinct from central memory T cells (TCM) and circulating effector memory T cells (TEM). Recent studies have described populations of TRM cells in the skin, gut, lungs, and nervous tissue. However, it is becoming increasingly clear that the specific environment in which the TRM reside can further refine their phenotypical and functional properties. Here, we focus on the TRM cells that develop following respiratory infection and reside in the lungs and the lung airways. Specifically, we will review recent studies that have described some of the requirements for establishment of TRM cells in these tissues, and the defining characteristics of TRM in the lungs and lung airways. With continual bombardment of the respiratory tract by both pathogenic and environmental antigens, dynamic fluctuations in the local milieu including homeostatic resources and niche restrictions can impact TRM longevity. Beyond a comprehensive characterization of lung TRM cells, special attention will be placed on studies, which have defined how the microenvironment of the lung influences memory T cell survival at this site. As memory T cell populations in the lung airways are requisite for protection yet wane numerically over time, developing a comprehensive picture of factors which may influence TRM development and persistence at these sites is important for improving T cell-based vaccine design.

An altered endometrial CD8 tissue resident memory T cell population in recurrent miscarriage

“…Low levels of CD127 are also found in CD8-Trm in the lung43, which may be associated with decreased maintenance of memory cells in this tissue. Further work is required to determine the survival capacity of human endometrial CD8-Trm as other signals could be responsible for their proliferation and survival like those postulated for lung Trm44. CD127 was significantly higher on CD69− versus CD69+ cells (p < 0.01) in controls, indicating CD69+ Trm are less likely to respond to IL-7 than other memory cells, which could indicate they are less likely to survive.…”

Original Antigenic Sin Response to RNA Viruses and Antiviral Immunity

“…Protection against the influenza virus through CD4 and CD8 T cell immunity alone was demonstrated in mice (4647). However, although memory CD4 and CD8 cells persist for a long time through homeostatic proliferation (1048), cross-protective resident memory CD8 T cells in pulmonary tissues, which are specific for the influenza virus, were shown to be short-lived (495051). These observations from experiments using mice have limitations; however, they appear to partly explain why infections recur, regardless of conserved epitopes of internal influenza proteins that can potentially generate universally protective memory CD8 T cells.…”

Tuberculosis vaccines: barriers and prospects on the quest for a transformative tool

“…Trms are long‐lived and well poised for early microbial interdiction, either directly or through recruiting additional effector T cells in an antigen‐dependent manner. Because of these properties, it is conceivable that strategies that deliberately aim to establish Trm in the lung might increase vaccine efficiency . One such possibility would be via the use of the recently developed cytomegalovirus (CMV) vaccine vector used in SIV/HIV vaccine research that induces large numbers of class II‐ and HLA‐E‐restricted CD8 + T cells in tissues throughout the body (, L. Picker, personal communication).…”