Early dynamic accumulation of tissue resident memory T cells in the human lung during infancy

Abstract

Abstract Infants exhibit increased susceptibility to viral and bacterial pathogens with pulmonary infections representing one of the top causes of infant mortality worldwide. Optimal protection from pathogens is mediated by coordinated functions of different T cell subsets, with tissue resident populations maintaining site-specific immunity in the respiratory tract. Currently, little is known of how tissue localized T cells populate and mediate mucosal immune responses in early life in humans. Here we analyzed T cell populations in the lungs obtained from infant and pediatric organ donors aged 8 days postnatal (PN) to 8 years by imaging and flow cytometry. In the earliest stage of life at 8 days PN, few αβ T cells were present in the lung, while innate-type γδ T cells were present around the airways. During the first two years of life, αβ T cells exhibiting memory phenotypes preferentially accumulated around the central airways and expressed canonical markers of tissue residency (CD69 and CD103), consistent with flow cytometry data. By contrast, the total number of γδ T cells in the lung did not change significantly with age for up to 8 years of life; for example, the ratio of αβ:γδ T cells in neonatal donors was 1.5:1, which increased to 16:1 in lungs of a 3 year old donor. Consistent with the imaging data, the frequency of γδ T cells by flow cytometry was significantly reduced after the early neonatal period. These results show that γδ T cells populate the lung during the early neonatal period and are maintained in relatively constant numbers over childhood, while tissue resident αβ T cells accumulate over first 2 years of life and predominate thereafter. Our results demonstrate the dynamic nature of lung-localized T cell immune responses in a mucosal site.