Interplay of Inflammatory, Antigen and Tissue-Derived Signals in the Development of Resident CD8 Memory T Cells

CD8 positive, tissue resident memory T cells (TRM) are a specialized subset of CD8 memory T cells that surveil tissues and provide critical first-line protection against tumors and pathogen re-infection. Recently, much effort has been dedicated to understanding the function, phenotype and development of TRM. A myriad of signals is involved in the development and maintenance of resident memory T cells in tissue. Much of the initial research focused on the roles tissue-derived signals play in the development of TRM, including TGFß and IL-33 which are critical for the upregulation of CD69 and CD103. However, more recent data suggest further roles for antigenic and pro-inflammatory cytokines. This review will focus on the interplay of pro-inflammatory, tissue and antigenic signals in the establishment of resident memory T cells.

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CXCR6 regulates localization of tissue-resident memory CD8 T cells to the airways

Journal of Experimental Medicine ◽

10.1084/jem.20181308 ◽

2019 ◽

Vol 216 (12) ◽

pp. 2748-2762 ◽

Cited By ~ 35

Author(s):

Alexander N. Wein ◽

Sean R. McMaster ◽

Shiki Takamura ◽

Paul R. Dunbar ◽

Emily K. Cartwright ◽

...

Keyword(s):

T Cells ◽

Cd8 T Cells ◽

Protective Immunity ◽

Memory T Cells ◽

Respiratory Pathogens ◽

First Line ◽

Memory Cd8 T Cells ◽

Effector Functions ◽

Signaling Axis ◽

Resident Memory T Cells

Resident memory T cells (TRM cells) are an important first-line defense against respiratory pathogens, but the unique contributions of lung TRM cell populations to protective immunity and the factors that govern their localization to different compartments of the lung are not well understood. Here, we show that airway and interstitial TRM cells have distinct effector functions and that CXCR6 controls the partitioning of TRM cells within the lung by recruiting CD8 TRM cells to the airways. The absence of CXCR6 significantly decreases airway CD8 TRM cells due to altered trafficking of CXCR6−/− cells within the lung, and not decreased survival in the airways. CXCL16, the ligand for CXCR6, is localized primarily at the respiratory epithelium, and mice lacking CXCL16 also had decreased CD8 TRM cells in the airways. Finally, blocking CXCL16 inhibited the steady-state maintenance of airway TRM cells. Thus, the CXCR6/CXCL16 signaling axis controls the localization of TRM cells to different compartments of the lung and maintains airway TRM cells.

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Brain-resident memory T cells represent an autonomous cytotoxic barrier to viral infection

Journal of Experimental Medicine ◽

10.1084/jem.20151916 ◽

2016 ◽

Vol 213 (8) ◽

pp. 1571-1587 ◽

Cited By ~ 86

Author(s):

Karin Steinbach ◽

Ilena Vincenti ◽

Mario Kreutzfeldt ◽

Nicolas Page ◽

Andreas Muschaweckh ◽

...

Keyword(s):

T Cells ◽

Viral Infection ◽

Immune Cell ◽

Memory T Cells ◽

Mhc I ◽

Brain Infection ◽

Cognate Antigen ◽

Resident Memory T Cells ◽

Pathogen Clearance ◽

Cd8 Memory T Cells

Tissue-resident memory T cells (TRM) persist at sites of prior infection and have been shown to enhance pathogen clearance by recruiting circulating immune cells and providing bystander activation. Here, we characterize the functioning of brain-resident memory T cells (bTRM) in an animal model of viral infection. bTRM were subject to spontaneous homeostatic proliferation and were largely refractory to systemic immune cell depletion. After viral reinfection in mice, bTRM rapidly acquired cytotoxic effector function and prevented fatal brain infection, even in the absence of circulating CD8+ memory T cells. Presentation of cognate antigen on MHC-I was essential for bTRM-mediated protective immunity, which involved perforin- and IFN-γ–dependent effector mechanisms. These findings identify bTRM as an organ-autonomous defense system serving as a paradigm for TRM functioning as a self-sufficient first line of adaptive immunity.

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