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Primate resident memory T cells activate humoral and stromal immunity [CITE-seq]

ABSTRACT: CD8 resident memory T cells (Trm) comprise a small population of frontline sentinels compared to the large tissues they surveil. CD8 Trm make outsized contributions to immune protection from infection, yet underlying mechanisms are not well understood. This study interrogated mechanisms of Trm function in primates. We show that intravenous immunization of macaques with an SIV-gag-containing heterologous prime-boost-boost vaccine establishes memory T cells in >30 tissues, including visceral and mucosal compartments. We next developed methods for reproductive tract CD8 Trm reactivation in vivo. Upon antigen-sensing, CD8 Trm activated local stromal, parenchymal, and innate and adaptive immune cells. Stromal and parenchymal cells accentuated leukocyte homing and antiviral defenses. B and plasma cells were mobilized in the vaginal mucosa and bloodborne CD4 T cells were recruited and adopted an infection-resistant phenotype. In conclusion, Trm repurpose abundant neighboring stromal, parenchymal, and immune cells to amplify alarm signals and activate diverse host defenses.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE255903 | GEO | 2025/12/04

REPOSITORIES: GEO

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Primate resident memory T cells activate humoral and stromal immunity [Bulk RNA-seq]

Project description:CD8 resident memory T cells (Trm) comprise a small population of frontline sentinels compared to the large tissues they surveil. CD8 Trm make outsized contributions to immune protection from infection, yet underlying mechanisms are not well understood. This study interrogated mechanisms of Trm function in primates. We show that intravenous immunization of macaques with an SIV-gag-containing heterologous prime-boost-boost vaccine establishes memory T cells in >30 tissues, including visceral and mucosal compartments. We next developed methods for reproductive tract CD8 Trm reactivation in vivo. Upon antigen-sensing, CD8 Trm activated local stromal, parenchymal, and innate and adaptive immune cells. Stromal and parenchymal cells accentuated leukocyte homing and antiviral defenses. B and plasma cells were mobilized in the vaginal mucosa and bloodborne CD4 T cells were recruited and adopted an infection-resistant phenotype. In conclusion, Trm repurpose abundant neighboring stromal, parenchymal, and immune cells to amplify alarm signals and activate diverse host defenses.

2025-12-04 | GSE256532 | GEO

Dynamic landscapes and protective immunity coordinated by influenza-specific lung-resident memory CD8+ T cells revealed by intravital imaging

Project description:Lung tissue-resident memory CD8+ T-cells (Trm) are critical for heterosubtypic immunity against influenza virus-(IAV)-reinfection. How these cells surveil the lung, respond to infection and interact with other cells remains unresolved. Here, we used mouse models to identify and enrich lung Trm in combination with intravital and static imaging to assess spatiotemporal dynamics of IAV-induced lung TRM before and after recall-infection. CD69+CD103+ Trm localize to sites of prior influenza infection where they exhibit substantially slower movement properties than non-Trm that also surveil the lung. After rechallenge, lung Trm form tight clusters in an antigen-dependent manner. IAV-specific Trm express several factors that regulate myeloid cell biology and their protective immune responses are accompanied by activation and migration of dendritic cells to draining lymph nodes and recruitment of inflammatory monocytes. Overall, these data reveal the dynamic landscapes of lung Trm cells associated with early protective immunity against IAV infection.

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Molecular signature of brain resident memory CD8+ T cells

Project description:Tissue resident memory (Trm) represent a newly described memory T cell population. We have previously characterized a population of Trm that persists within the brain following acute virus infection. Although capable of providing marked protection against a subsequent local challenge, brain Trm do not undergo recall expansion following dissociation from the tissue. Furthermore, these Trm do not depend on the same survival factors as the circulating memory T cell pool as assessed either in vivo or in vitro. To gain greater insight into this population of cells we compared the gene-expression profiles of Trm isolated from the brain to circulating memory T cells isolated from the spleen following an acute virus infection. Trm displayed altered expression of genes involved in chemotaxis, expressed a distinct set of transcription factors and overexpressed several inhibitory receptors. Cumulatively, these data indicates that Trm are a distinct memory T cell population disconnected from the circulating memory T cell pool and displaying a unique molecular signature which likely results in optimal survival and function within their local environment. 13 samples were analyzed: 5 replicates of memory OT-I CD8+.CD103- T cells isolated from the spleen of mice on day 20 p.i. with VSV-OVA. 5 replicates of memory OT-I CD8+CD103+ T cells isolated from the brain of mice on day 20 p.i. with VSV-OVA; and 3 replicates of memory OT-I.CD8+ CD103- T cells isolated from the brain of mice on day 20 p.i. with VSV-OVA

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2017-06-12 | GSE95105 | GEO

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Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets II

Project description:Tissue-resident memory T (TRM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However transcriptional heterogeneity of human intestinal TRM cells remains undefined. Here, we investigated transcriptional and functional heterogeneity of human TRM cells through study of donor-derived intestinal TRM cells from intestinal transplant recipients. Single-cell transcriptional profiling identified two distinct transcriptional states of CD8+ TRM cells, delineated by ITGAE and ITGB2 expression. We defined a transcriptional signature discriminating these two CD8+ populations, including differential expression of cytotoxicity- and residency-associated genes. Flow cytometry of recipient-derived cells infiltrating the graft and lymphocytes from healthy gut confirmed the two CD8+ TRM phenotypes. CD103+ CD8+ TRM cells produced IL-2, and demonstrated greater polyfunctional cytokine production, while β2-integrin+ CD69+ CD103- TRM cells had higher granzyme expression. Phenotypic and functional analysis of intestinal CD4+ T cells identified many parallels, including a distinct β2-integrin+ population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal CD4+ and CD8+ TRM cells.

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