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    Oja, A E; Piet, B; Helbig, C; Stark, R; van der Zwan, D; Blaauwgeers, H; Remmerswaal, E B M; Amsen, D; Jonkers, R E; Moerland, P D; Nolte, M A; van Lier, R A W; Hombrink, P

    Mucosal immunology, 05/2018, Letnik: 11, Številka: 3
    Journal Article

    Resident memory T cells (T ) reside in the lung epithelium and mediate protective immunity against respiratory pathogens. Although lung CD8 T have been extensively characterized, the properties of CD4 T remain unclear. Here we determined the transcriptional signature of CD4 T , identified by the expression of CD103, retrieved from human lung resection material. Various tissue homing molecules were specifically upregulated on CD4 T , whereas expression of tissue egress and lymph node homing molecules were low. CD103 T 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 T showed a Notch signature. CD4 CD103 T 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 T in the human lung. Understanding the specific properties of CD4 T is required to rationally improve vaccine design.