Memory CD8 + T Cells: Innate-Like Sensors and Orchestrators of Protection

Lauvau, Grégoire; Boutet, Marie; Williams, Tere; Chin, Shu Shien; Chorro, Laurent

doi:10.1016/j.it.2016.04.001

Cited by 32 publications

(30 citation statements)

References 82 publications

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“…To test this hypothesis, we tested for differential gene expression between lung and liver single-cell profiles, which revealed tissue-specific genes in memory CD8 + T cells, including in cells with the same antigen specificity (B8R) ( Figures 7A and 7B). We validated these results at the protein level for CCL5, a welldescribed effector molecule in memory CD8 + T cells (Lauvau et al, 2016) and present in nearly all lung and liver cells; CX3CR1, which resolved two subpopulations in lung and liver; and CXCR6 and ITGA1, which showed liver-specific expression in subsets of cells ( Figures S7A and S7B), as recently shown for CXCR6 (Fernandez-Ruiz et al, 2016). In addition, a number of other surface molecules (e.g., Fcer1g), before splitting, whereas for group +14, mice were joined for 2 weeks before immunization of one parabiont and split after another 2 weeks.…”

Section: Tissue-resident Memory Cd8 + T Cells Are Activated Across Tisupporting

confidence: 53%

“…and performed scRNA-seq on B8R-specific memory CD8 + T cells. Differential expression analysis between B8R-treated and control animals identified a transcriptional signature including genes known to function in memory CD8 + T cell responses, such as Ifng, Gzmb, Xcl1, and Ccl4 (Figure 6C) (Lauvau et al, 2016). Importantly, the average expression of B8R peptide-induced genes (referred to as B8R activation score) was significantly higher in tetramer positive versus negative cells upon B8R peptide challenge (p value = 1.64 3 10 À6 ) ( Figure S6A).…”

Section: Tissue-resident Memory Cd8 + T Cells Are Activated Across Timentioning

confidence: 99%

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Organism-Level Analysis of Vaccination Reveals Networks of Protection across Tissues

Kadoki

Patil

Thaiss

et al. 2017

Cell

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A fundamental challenge in immunology is to decipher the principles governing immune responses at the whole-organism scale. Here, using a comparative infection model, we observe immune signal propagation within and between organs to obtain a dynamic map of immune processes at the organism level. We uncover two inter-organ mechanisms of protective immunity mediated by soluble and cellular factors. First, analyzing ligand-receptor connectivity across tissues reveals that type I IFNs trigger a whole-body antiviral state, protecting the host within hours after skin vaccination. Second, combining parabiosis, single-cell analyses, and gene knockouts, we uncover a multi-organ web of tissue-resident memory T cells that functionally adapt to their environment to stop viral spread across the organism. These results have implications for manipulating tissue-resident memory T cells through vaccination and open up new lines of inquiry for the analysis of immune responses at the organism level.

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Section: Tissue-resident Memory Cd8 + T Cells Are Activated Across Tisupporting

confidence: 53%

Section: Tissue-resident Memory Cd8 + T Cells Are Activated Across Timentioning

confidence: 99%

Organism-Level Analysis of Vaccination Reveals Networks of Protection across Tissues

Kadoki

Patil

Thaiss

et al. 2017

Cell

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“…Among the many different cell types capable of chemokine production, pathogen-specific T cells were identified as a relevant source over two decades ago [16]. However, while the T cell-produced chemokines CCL3/4/5 have received considerable attention as competitive inhibitors of HIV binding to its co-receptor CCR5 [17][18][19], an inclusive perspective on specific T cell-produced chemokines has not been established, a likely consequence of both an experimental and conceptual emphasis on chemokine action on T cells rather than chemokine production by T cells [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Chemokine Signatures Of Pathogen-Specific T Cells I: Effector T Cells

Eberlein

Davenport

Nguyen

et al. 2020

Preprint

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The choreography of complex immune responses, including the priming, differentiation, and modulation of specific effector T cell populations generated in the immediate wake of an acute pathogen challenge, is in part controlled by chemokines, a large family of mostly secreted molecules involved in chemotaxis and other patho/physiological processes. T cells are both responsive to varied chemokine cues and a relevant source for certain chemokines themselves. Yet the actual range, regulation, and role of effector T cell-derived chemokines remains incompletely understood. Here, using different in vivo models of viral and bacterial infection as well as protective vaccination, we have defined the entire spectrum of chemokines produced by pathogen-specific CD8+ and CD4+T effector cells, and delineated several unique properties pertaining to the temporospatial organization of chemokine expression patterns, synthesis and secretion kinetics, and cooperative regulation. Collectively, our results position the “T cell chemokine response” as a notably prominent, largely invariant yet distinctive force at the forefront of pathogen-specific effector T cell activities, and establish novel practical and conceptual approaches that may serve as a foundation for future investigations into role of T cell-produced chemokines in infectious and other diseases.

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“…One possibility is that the wrong types of T cells, either functionally or spatially, are being induced. Memory T cells can be phenotypically characterized by their cell surface marker expression, with different subsets behaving differently on re-exposure to the pathogen 9 . Recently a novel population of tissue resident memory T (Trm) cells has been defined.…”

Section: Introductionmentioning

confidence: 99%

Airway T cells protect against RSV infection in the absence of antibody

et al. 2018

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Tissue resident memory T cells (Trm) act as sentinels and early responders to infection. RSV specific Trm have been detected in the lungs after human RSV infection, but whether they play a protective role is unknown. To dissect the protective function of Trm, BALB/c mice were infected with RSV; infected mice developed antigen specific CD8 + Trm (CD103 + /CD69 + ) in the lungs and airways.Intranasally transferring cells from the airways of previously infected animals to naïve animals reduced weight loss on infection in the recipient mice. Transfer of airway CD8 cells led to reduced disease and viral load and increased IFNγ in the airways of recipient mice, whilst CD4 transfer reduced TNFα in the airways. Because DNA vaccines induce a systemic T cell response, we compared vaccination with infection for the effect of memory CD8 cells generated in different compartments. Intramuscular DNA immunization induced RSV specific CD8 T cells, but they were immunopathogenic not protective. Notably, there was a marked difference in the induction of Trm; infection but not immunization induced antigen specific Trm in a range of tissues. These findings demonstrate a protective role for airway CD8 against RSV and support the need for vaccines to induce antigen specific airway cells.3

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Memory CD8 + T Cells: Innate-Like Sensors and Orchestrators of Protection

Cited by 32 publications

References 82 publications

Organism-Level Analysis of Vaccination Reveals Networks of Protection across Tissues

Organism-Level Analysis of Vaccination Reveals Networks of Protection across Tissues

Chemokine Signatures Of Pathogen-Specific T Cells I: Effector T Cells

Airway T cells protect against RSV infection in the absence of antibody

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