Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites

• Main Authors: Brahma V. Kumar, Wenji Ma, Michelle Miron, Tomer Granot, Rebecca S. Guyer, Dustin J. Carpenter, Takashi Senda, Xiaoyun Sun, Siu-Hong Ho, Harvey Lerner, Amy L. Friedman, Yufeng Shen, Donna L. Farber
• Format: Article
• Language: English
• Published: Elsevier 2017-09-01
• Series: Cell Reports
• Subjects: human immunology; memory T cells; RNA-seq; mucosal immunity
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124717312202

Tissue-resident memory T cells (TRMs) in mice mediate optimal protective immunity to infection and vaccination, while in humans, the existence and properties of TRMs remain unclear. Here, we use a unique human tissue resource to determine whether human tissue memory T cells constitute a distinct subset in diverse mucosal and lymphoid tissues. We identify a core transcriptional profile within the CD69+ subset of memory CD4+ and CD8+ T cells in lung and spleen that is distinct from that of CD69− TEM cells in tissues and circulation and defines human TRMs based on homology to the transcriptional profile of mouse CD8+ TRMs. Human TRMs in diverse sites exhibit increased expression of adhesion and inhibitory molecules, produce both pro-inflammatory and regulatory cytokines, and have reduced turnover compared with circulating TEM, suggesting unique adaptations for in situ immunity. Together, our results provide a unifying signature for human TRM and a blueprint for designing tissue-targeted immunotherapies.