1. Trigger-happy resident memory CD4(+) T cells inhabit the human lungs
- Author
-
Anna E. Oja, Regina Stark, Derk Amsen, R. A. W. Van Lier, Martijn A. Nolte, Ester B. M. Remmerswaal, René E. Jonkers, H Blaauwgeers, Pleun Hombrink, Berber Piet, Perry D. Moerland, Christina Helbig, D van der Zwan, AII - Inflammatory diseases, Experimental Immunology, AII - Amsterdam institute for Infection and Immunity, Landsteiner Laboratory, Pulmonology, APH - Personalized Medicine, APH - Methodology, and Epidemiology and Data Science
- Subjects
0301 basic medicine ,Regulation of gene expression ,medicine.medical_treatment ,Immunology ,Eomesodermin ,chemical and pharmacologic phenomena ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,Biology ,Cell biology ,Transcriptome ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Cytokine ,Interferon ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,CD8 ,030215 immunology ,Homing (hematopoietic) ,medicine.drug - Abstract
Resident memory T cells (TRM) reside in the lung epithelium and mediate protective immunity against respiratory pathogens. Although lung CD8(+) TRM have been extensively characterized, the properties of CD4(+) TRM remain unclear. Here we determined the transcriptional signature of CD4(+) TRM, identified by the expression of CD103, retrieved from human lung resection material. Various tissue homing molecules were specifically upregulated on CD4(+) TRM, whereas expression of tissue egress and lymph node homing molecules were low. CD103(+) TRM expressed low levels of T-bet, only a small portion expressed Eomesodermin (Eomes), and although the mRNA levels for Hobit were increased, protein expression was absent. On the other hand, the CD103(+) TRM showed a Notch signature. CD4(+)CD103(+) TRM constitutively expressed high transcript levels of numerous cytotoxic mediators that was functionally reflected by a fast recall response, magnitude of cytokine production, and a high degree of polyfunctionality. Interestingly, the superior cytokine production appears to be because of an accessible interferon-γ (IFNγ) locus and was partially because of rapid translation of preformed mRNA. Our studies provide a molecular understanding of the maintenance and potential function of CD4(+) TRM in the human lung. Understanding the specific properties of CD4(+) TRM is required to rationally improve vaccine design.Mucosal Immunology advance online publication 15 November 2017; doi:10.1038/mi.2017.94
- Published
- 2018
- Full Text
- View/download PDF