T Cell Responsiveness Through the Ages: Functional Diversity of Age-Dependent Antiviral Responses
type: CreativeWork
description: An organism’s age impacts its susceptibility to disease, which varies according to the type of insult or causal pathogen. Much work remains to delineate these complexities, especially within younger individuals. Indeed, pediatric disease-driven immunity is less characterized than adult and aging populations due to two main factors: 1) descriptions through multiple stages of development are required, as the immune system undergoes massive changes from gestation through the end of adolescence, and 2) the complex nature of pediatric research decreases the availability of robust and comprehensive studies. Importantly, studying the immune system in relation to age requires a foundational knowledge within adult individuals to adequately assess the unique characteristics of the developing and aged systems. This body of work contributes to the field of age-dependent immunity via the study of repair-associated T cell subsets in pediatric acute respiratory distress syndrome (pARDS), γδ T cells in murine cytomegalovirus (MCMV), and multiple immune mediators and cell populations in adult severe influenza infection. Single-cell RNA sequencing of tracheal aspirate cells from pediatric subjects experiencing acute respiratory failure (ARF) showed that distinct T cell subsets within the lower respiratory tract exhibited transcriptional similarity, termed functional redundancy. This similarity was repair-associated, and a defining gene of the transcriptional profile was amphiregulin (AREG). When quantified, T cells from subjects with a viral lower respiratory tract infection (LRTI) that did not progress to moderate or severe pARDS had significantly elevated repair scores. This was reflected within tissue resident memory (TRM) CD8 T cells, activated regulatory CD4 T cells (Tregs), and activated AREG+ γδ T cells. The repair profile was then applied across publicly available datasets spanning ages, tissue types, etiologies, and severities, and functional redundancy was only observed wit…
abstract: An organism’s age impacts its susceptibility to disease, which varies according to the type of insult or causal pathogen. Much work remains to delineate these complexities, especially within younger individuals. Indeed, pediatric disease-driven immunity is less characterized than adult and aging populations due to two main factors: 1) descriptions through multiple stages of development are required, as the immune system undergoes massive changes from gestation through the end of adolescence, and 2) the complex nature of pediatric research decreases the availability of robust and comprehensive studies. Importantly, studying the immune system in relation to age requires a foundational knowledge within adult individuals to adequately assess the unique characteristics of the developing and aged systems. This body of work contributes to the field of age-dependent immunity via the study of repair-associated T cell subsets in pediatric acute respiratory distress syndrome (pARDS), γδ T cells in murine cytomegalovirus (MCMV), and multiple immune mediators and cell populations in adult severe influenza infection. Single-cell RNA sequencing of tracheal aspirate cells from pediatric subjects experiencing acute respiratory failure (ARF) showed that distinct T cell subsets within the lower respiratory tract exhibited transcriptional similarity, termed functional redundancy. This similarity was repair-associated, and a defining gene of the transcriptional profile was amphiregulin (AREG). When quantified, T cells from subjects with a viral lower respiratory tract infection (LRTI) that did not progress to moderate or severe pARDS had significantly elevated repair scores. This was reflected within tissue resident memory (TRM) CD8 T cells, activated regulatory CD4 T cells (Tregs), and activated AREG+ γδ T cells. The repair profile was then applied across publicly available datasets spanning ages, tissue types, etiologies, and severities, and functional redundancy was only observed wit…
author: Clark, Brandi L.
keywords: Age;Influenza;MCMV;pARDS;T cell;γδ T cell, Medicine and Health Sciences
date published: 2023-12-01T08:00:00Z
date modified: 2026-07-24T05:00:53Z
provider: University of Tennessee Health Science Center
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Tennessee Health Science Center