Abstract
Tissue-resident CD8+ T cells (CD8+ TRM) populate lymphoid and non-lymphoid tissues after infections as first line of defense against re-emerging pathogens. To achieve host protection, CD8+ TRM have developed surveillance strategies that combine dynamic interrogation of pMHC complexes on local stromal and hematopoietic cells with long-term residency. Factors mediating CD8+ TRM residency include CD69, a surface receptor opposing the egress-promoting S1P1, CD49a, a collagen-binding integrin, and CD103, which binds E-cadherin on epithelial cells. Moreover, the topography of the tissues of residency may influence TRM retention and surveillance strategies. Here, we provide a brief summary of these factors to examine how CD8+ TRM reconcile constant migratory behavior with their long-term commitment to local microenvironments, with a focus on epithelial barrier organs and exocrine glands with mixed connective—epithelial tissue composition.
Highlights
Ag-specific naïve CD8+ T cells (TN) become activated in reactive secondary lymphoid organs (SLOs), and change their gene expression pattern and metabolism to differentiate into proliferating cytotoxic effector T cells (TEFF) [1, 2]
TEFF killing of infected cells in inflamed tissue requires direct cell-to-cell contact to identify cognate peptide major histocompatibility complexes on target cells, which leads to release of granzymes and perforin for induction of apoptosis [4, 5]
Central memory T cells (TCM) maintain the ability to recirculate through SLOs through expression of the homing receptors Lselectin (CD62L) and the chemokine receptor CCR7, a characteristic shared with TN
Summary
Ag-specific naïve CD8+ T cells (TN) become activated in reactive secondary lymphoid organs (SLOs), and change their gene expression pattern and metabolism to differentiate into proliferating cytotoxic effector T cells (TEFF) [1, 2]. While the high expression of CD69, CD49a, and RGS1 on a majority of non-barrier NLT TRM suggests similar roles as in epithelial barrier tissues, CD103 expression is not required for long-term retention of TRM in SMG, in contrast to skin [81, 82] Another key issue is whether memory T cells from distinct anatomical locations employ tissue-specific mechanisms of host surveillance. The scanning strategy adopted by homeostatic SMG TRM resembles the migration pattern of T cell blasts in 3D collagen networks, where these cells routinely bypass dense collagen areas, while probing the environment for permissive gaps for cell body translocation [93] These observations are consistent with a model where certain NLT TRM switch during homeostatic immune surveillance to a self-motile “autopilot” mode supported by tissue macrophage topography, while remaining susceptible to locally produced inflammatory signals for concerted cytotoxic activity. Combining in vivo analysis with high resolution single cell technologies to take into account cell heterogeneity will shed light on these open points
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