Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands

Duckworth, Brigette C.; Lafouresse, Fanny; Wimmer, Verena C.; Broomfield, Benjamin J; Dalit, Lennard; Alexandre, Yannick O.; Sheikh, Amania A; Qin, Raymond Z.; Alvarado, Carolina; Mielke, Lisa A.; Pellegrini, Marc; Mueller, Scott N.; Boudier, Thomas; Rogers, Kelly L.; Groom, Joanna R

doi:10.1038/s41590-021-00878-5

Cited by 75 publications

(168 citation statements)

References 58 publications

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“…17,30,53 Delving into this further, we showed that TCF-1, the key transcriptional regulator of T SCM cells, binds to the Ccr7 locus. 138 Supporting this, multiple studies have demonstrated that CCR7 is downregulated in the absence of TCF-1 or in T cell populations that lack TCF-1. 27,53,165 The retained expression of CCR7 on T SCM is in contrast to T FH cells, where this receptor is downregulated rapidly following the upregulation of Bcl6.…”

Section: Differentiation Of T Scm Cells In the Center Of Lymph Nodesmentioning

confidence: 87%

“…7 While this study did not reveal the precise dendritic cell or stromal cell population that move T cells into this area, we have now demonstrated that type 2 conventional dendritic cells (cDC2) express high levels CXCL10 in the IFR. 138 Similar to CD4+ T H1 differentiation, CD8+ effectors are also found in IFRs and this migration correlates with robust formation of effector function. 139 CD8+ T cells in IFRs form clusters around cDC2 cells consistent with their expression of CXCL10.…”

Section: F I G U R Ementioning

confidence: 90%

“…While these cells highly express CXCL9, loss of CXCL9 does not appear to alter T SCM differentiation in vivo. 138 Previous work has shown that these interactions are alternatively instructed by CCR5. 167 Unlike cDC2s, cDC1s are thought to be a more homogeneous population 133 ; however, it could be that subsets of dendritic cells with a defined imprinting potential reside in the paracortex.…”

Section: Differentiation Of T Scm Cells In the Center Of Lymph Nodesmentioning

confidence: 98%

“…49,143 We have shown the first observable expression of T-bet in CD8+ T cells is found within pockets of IFRs; however, it is likely that moderate T-bet induction is sufficient for CXCR3 expression and migration into this region. 138 While CD8+ T cells and cDC2s cluster in IFRs, it is unclear if this interaction is mediated through cDC2-derived CXCL10, or if stromal cell expression moves T cells into this region. We have shown that CD4+ T cells preferentially interact with CXCL10+ expressing DCs, but the specific location of these interactions and the DC subset was not defined in this study.…”

Section: F I G U R Ementioning

confidence: 99%

“…24 To clarify this discrepancy, we have shown that the T SCM precursors are retained in the T cell zone following viral infection, and their differentiation is enhanced in the absence of CXCR3. 138 While the transcriptional regulation of T cell effector molecules is well established, less attention has been placed on the transcriptional regulators of T cell location. 17,30,53 Delving into this further, we showed that TCF-1, the key transcriptional regulator of T SCM cells, binds to the Ccr7 locus.…”

Section: Differentiation Of T Scm Cells In the Center Of Lymph Nodesmentioning

confidence: 99%

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Conversations that count: Cellular interactions that drive T cell fate

Duckworth

Groom

2021

Immunological Reviews

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The activation and differentiation of T cells play an essential role in orchestrating adaptive immune responses. These interactions determine how responses are tailored toward the pathogen and the success of T cell responses; whether pathogens or cancer cells are eliminated by effector cells, and if immunological memory is generated for longlasting protection. The paths to each of these outcomes are determined by the cells that T cells interact with during their activation. A key feature of immune cells is their motility. T cell migration is primarily driven by chemokines and their chemokine receptors, which coordinate cell migration into specific sites and promote T cell interactions. 1,2 Naive T cells that are single positive for either CD4 or CD8 enter circulation following their maturation in the thymus. 3 Upon their arrival in the secondary lymphoid organs, such as the spleen and lymph nodes, T cells seek out interactions with dendritic cells to search for the presentation of their cognate antigen. 4-6 Work from our group, and others has demonstrated that where these

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Section: Differentiation Of T Scm Cells In the Center Of Lymph Nodesmentioning

confidence: 87%

Section: F I G U R Ementioning

confidence: 90%

Section: Differentiation Of T Scm Cells In the Center Of Lymph Nodesmentioning

confidence: 98%

Section: F I G U R Ementioning

confidence: 99%

Section: Differentiation Of T Scm Cells In the Center Of Lymph Nodesmentioning

confidence: 99%

See 3 more Smart Citations

Conversations that count: Cellular interactions that drive T cell fate

Duckworth

Groom

2021

Immunological Reviews

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Compartmentalized multicellular crosstalk in lymph nodes coordinates the generation of potent cellular and humoral immune responses

et al. 2021

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Distributed throughout the body, lymph nodes (LNs) constitute an important crossroad where resident and migratory immune cells interact to initiate antigen-specific immune responses supported by a dynamic 3-dimensional network of stromal cells, that is, endothelial cells and fibroblastic reticular cells (FRCs). LNs are organized into four major subanatomically separated compartments: the subcapsular sinus (SSC), the paracortex, the cortex, and the medulla. Each compartment is underpinned by particular FRC subsets that physically support LN architecture and delineate functional immune niches by appropriately providing environmental cues, nutrients, and survival factors to the immune cell subsets they interact with. In this review, we discuss how FRCs drive the structural and functional organization of each compartment to give rise to prosperous interactions and coordinate immune cell activities. We also discuss how reciprocal communication makes FRCs and immune cells perfect compatible partners for the generation of potent cellular and humoral immune responses.

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Dendritic cell functions in vivo: A user's guide to current and next‐ generation mutant mouse models

Dalod

Scheu

2022

Eur J Immunol

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DCs do not just excel in antigen presentation. They orchestrate information transfer from innate to adaptive immunity by sensing and integrating a variety of danger signals, and translating them to naïve T cells, to mount specifically tailored immune responses. This is accomplished by distinct DC types specialized in different functions and because each DC is functionally plastic, assuming different activation states depending on the input signals received. Mouse models hold the key to untangle this complexity and determine which DC types and activation states contribute to which functions. Here, we aim to provide comprehensive information for selecting the most appropriate mutant mouse strains to address specific research questions on DCs, considering three in vivo experimental approaches: (i) interrogating the roles of DC types through their depletion; (ii) determining the underlying mechanisms by specific genetic manipulations; (iii) deciphering the spatiotemporal dynamics of DC responses. We summarize the advantages, caveats, suggested use, and perspectives for a variety of mutant mouse strains, discussing in more detail the most widely used or accurate models. Finally, we discuss innovative strategies to improve targeting specificity and next-generation mutant mouse models, and briefly address how humanized mouse models can accelerate translation into the clinic.

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Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands

Cited by 75 publications

References 58 publications

Conversations that count: Cellular interactions that drive T cell fate

Conversations that count: Cellular interactions that drive T cell fate

Compartmentalized multicellular crosstalk in lymph nodes coordinates the generation of potent cellular and humoral immune responses

Dendritic cell functions in vivo: A user's guide to current and next‐ generation mutant mouse models

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