Journal Article

Programs for the persistence, vigilance and control of human CD8+ lung-resident memory T cells

Nota, Benjamin, Clevers, Hans C, Backer, Ronald A, Stark, Regina, Brasser, Giso, Oja, Anna E, Amsen, Derk, Piet, Berber, Hombrink, Pleun, Jongejan, Aldo, Jonkers, René E, van Lier, René A W, Helbig, Christina, Basak, Onur, Moerland, Perry D

2016

Overview

A goal of vaccination is to elicit and maintain tissue-resident memory T cells. Amsen and colleagues show human lung-resident memory CD8 + T cells express distinct transcriptional programs, including a role for Notch in cellular metabolism and maintenance. Tissue-resident memory T cells (T RM cells) in the airways mediate protection against respiratory infection. We characterized T RM cells expressing integrin α E (CD103) that reside within the epithelial barrier of human lungs. These cells had specialized profiles of chemokine receptors and adhesion molecules, consistent with their unique localization. Lung T RM cells were poised for rapid responsiveness by constitutive expression of deployment-ready mRNA encoding effector molecules, but they also expressed many inhibitory regulators, suggestive of programmed restraint. A distinct set of transcription factors was active in CD103 + T RM cells, including Notch. Genetic and pharmacological experiments with mice revealed that Notch activity was required for the maintenance of CD103 + T RM cells. We have thus identified specialized programs underlying the residence, persistence, vigilance and tight control of human lung T RM cells.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/1619/554/1834 / 631/250/2152/1566/1571 / Animals / Antigens, CD - metabolism / Biomedicine / CD103 antigen / CD8 antigen / CD8-Positive T-Lymphocytes - physiology / Cell adhesion molecules / Cells, Cultured / Chemokine receptors / Effector cells / Female / Gene expression / Humans / Immunologic Memory / Immunological memory / Immunology / Infectious Diseases / Influenza A Virus, H3N2 Subtype - immunology / Integrin alpha Chains - metabolism / Localization / Lung - immunology / Lungs / Lymphocytes / Lymphocytes T / Male / Memory cells / Mice / Mice, Inbred C57BL / Mice, Transgenic / Middle Aged / Orthomyxoviridae Infections - immunology / Receptor, Notch1 - genetics / Receptor, Notch1 - metabolism / Receptor, Notch2 - genetics / Receptor, Notch2 - metabolism / resource / Respiratory tract infection / Respiratory Tract Infections - immunology / Transcription factors / Vaccination / Vigilance