PD‐1: always on my mind

Park, Simone L.; Mackay, Laura K.

doi:10.1038/icb.2017.69

Cited by 4 publications

(5 citation statements)

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“…Our finding is in line with other work which demonstrates that the effector function of bT RM cells produced IFN-g both in situ and in response to ex vivo peptide stimulation [48]. It has been reported that treating T RM cells with PD-L1 blocking Abs results in increased cytokine production [47,48]. Our previous data report that blockade of the PD-1: PD-L1 pathway in both microglia and astrocyte: CD8 T-cell co-cultures resulted in increased IFN-g and IL-2 production [1].…”

Section: Discussionsupporting

confidence: 93%

“…Work presented here identifies the role of glial cells in bT RM development through PD‐1: PD‐L1 signaling. Within the brain, T RM cells have largely been defined by co‐expression of CD69 and CD103 .…”

Section: Discussionmentioning

confidence: 99%

“…Work presented here identifies the role of glial cells in bT RM development through PD-1: PD-L1 signaling. Within the brain, T RM cells have largely been defined by co-expression of CD69 and CD103 [46,47]. A significantly reduced frequency of MCMV-specific bT RM was seen within the brain of PD-L1 KO animals when compared to WT animals at d 30 p.i.…”

Section: Discussionmentioning

confidence: 99%

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Reactive glia promote development of CD103⁺CD69⁺ CD8⁺ T‐cells through programmed cell death‐ligand 1 (PD‐L1)

Prasad

Sheng

et al. 2018

Immunity Inflam & Disease

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IntroductionPrevious work from our laboratory has demonstrated in vivo persistence of CD103+CD69+ brain resident memory CD8+ T‐cells (bTRM) following viral infection, and that the PD‐1: PD‐L1 pathway promotes development of these TRM cells within the brain. Although glial cells express low basal levels of PD‐L1, its expression is upregulated upon IFN‐γ‐treatment, and they have been shown to modulate antiviral T‐cell effector responses through the PD‐1: PD‐L1 pathway.MethodsWe performed flow cytometric analysis of cells from co‐cultures of mixed glia and CD8+ T‐cells obtained from wild type mice to investigate the role of glial cells in the development of bTRM.ResultsIn this study, we show that interactions between reactive glia and anti‐CD3 Ab‐stimulated CD8+ T‐cells promote development of CD103+CD69+ CD8+ T‐cells through engagement of the PD‐1: PD‐L1 pathway. These studies used co‐cultures of primary murine glial cells obtained from WT animals along with CD8+ T‐cells obtained from either WT or PD‐1 KO mice. We found that αCD3 Ab‐stimulated CD8+ T‐cells from WT animals increased expression of CD103 and CD69 when co‐cultured with primary murine glial cells. In contrast, significantly reduced expression of CD103 and CD69 was observed using CD8+ T‐cells from PD‐1 KO mice. We also observed that reactive glia promoted high levels of CD127, a marker of memory precursor effector cells (MPEC), on CD69+ CD8+ T‐cells, which promotes development of TRM cells. Interestingly, results obtained using T‐cells from PD‐1 KO animals showed significantly reduced expression of CD127 on CD69+ CD8+ cells. Additionally, blocking of glial PD‐L1 resulted in decreased expression of CD103, along with reduced CD127 on CD69+ CD8+ T‐cells.ConclusionsTaken together, these results demonstrate a role for activated glia in promoting development of bTRM through the PD‐1: PD‐L1 pathway.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Reactive glia promote development of CD103⁺CD69⁺ CD8⁺ T‐cells through programmed cell death‐ligand 1 (PD‐L1)

Prasad

Sheng

et al. 2018

Immunity Inflam & Disease

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“…Although PD-1 is highly expressed by CD8 bT RM during encephalitis by MuPyV and MCMV ( 7 , 19 , 88 , 89 ), these bT RM do not display a clear exhaustion profile ( 19 , 90 , 91 ). Rather, PD-1 appears to operate in the brain primarily to balance bystander- and virus-induced inflammation and tissue damage against virus control by antiviral bT RM cells ( 90 , 91 ).…”

Section: Pd-1: An Arbiter Of Neuroprotectionmentioning

confidence: 99%

Balancing Inflammation and Central Nervous System Homeostasis: T Cell Receptor Signaling in Antiviral Brain TRM Formation and Function

2021

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Tissue-resident memory (TRM) CD8 T cells provide early frontline defense against regional pathogen reencounter. CD8 TRM are predominantly parked in nonlymphoid tissues and do not circulate. In addition to this anatomic difference, TRM are transcriptionally and phenotypically distinct from central-memory T cells (TCM) and effector-memory T cells (TEM). Moreover, TRM differ phenotypically, functionally, and transcriptionally across barrier tissues (e.g., gastrointestinal tract, respiratory tract, urogenital tract, and skin) and in non-barrier organs (e.g., brain, liver, kidney). In the brain, TRM are governed by a contextual milieu that balances TRM activation and preservation of essential post-mitotic neurons. Factors contributing to the development and maintenance of brain TRM, of which T cell receptor (TCR) signal strength and duration is a central determinant, vary depending on the infectious agent and modulation of TCR signaling by inhibitory markers that quell potentially pathogenic inflammation. This review will explore our current understanding of the context-dependent factors that drive the acquisition of brain (b)TRM phenotype and function, and discuss the contribution of TRM to promoting protective immune responses in situ while maintaining tissue homeostasis.

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“…PD-L1 also plays an important role in controlling secondary virus challenge as lack of PD-L1 resulted in functional defect in bT RM -mediated virus control in knock-out animals [43]. Reports also indicate that treating bT RM with anti-PD-L1 results in increased production of inflammatory cytokines [38,44]. Hence, PD-L1 not only influences the accumulation of virus-specific T RM but also affects their cytokine production in the brain.…”

Section: Role Of Pd-l1 In the Development Of Brain-resident Memorymentioning

confidence: 99%

Glial Cell Expression of PD-L1

Chauhan

Lokensgard

2019

IJMS

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The programmed death (PD)-1/PD-L1 pathway is a well-recognized negative immune checkpoint that results in functional inhibition of T-cells. Microglia, the brain-resident immune cells are vital for pathogen detection and initiation of neuroimmune responses. Moreover, microglial cells and astrocytes govern the activity of brain-infiltrating antiviral T-cells through upregulation of PD-L1 expression. While T-cell suppressive responses within brain are undoubtedly beneficial to the host, preventing cytotoxic damage to this vital organ, establishment of a prolonged anti-inflammatory milieu may simultaneously lead to deficiencies in viral clearance. An immune checkpoint blockade targeting the PD-1: PD-L1 (B7-H1; CD274) axis has revolutionized contemporary treatment for a variety of cancers. However, the therapeutic potential of PD1: PD-L1 blockade therapies targeting viral brain reservoirs remains to be determined. For these reasons, it is key to understand both the detrimental and protective functions of this signaling pathway within the brain. This review highlights how glial cells use PD-L1 expression to modulate T-cell effector function and limit detrimental bystander damage, while still retaining an effective defense of the brain.

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PD‐1: always on my mind

Cited by 4 publications

References 10 publications

Reactive glia promote development of CD103⁺CD69⁺ CD8⁺ T‐cells through programmed cell death‐ligand 1 (PD‐L1)

Reactive glia promote development of CD103⁺CD69⁺ CD8⁺ T‐cells through programmed cell death‐ligand 1 (PD‐L1)

Balancing Inflammation and Central Nervous System Homeostasis: T Cell Receptor Signaling in Antiviral Brain TRM Formation and Function

Glial Cell Expression of PD-L1

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PD‐1: always on my mind

Cited by 4 publications

References 10 publications

Reactive glia promote development of CD103+CD69+ CD8+ T‐cells through programmed cell death‐ligand 1 (PD‐L1)

Reactive glia promote development of CD103+CD69+ CD8+ T‐cells through programmed cell death‐ligand 1 (PD‐L1)

Balancing Inflammation and Central Nervous System Homeostasis: T Cell Receptor Signaling in Antiviral Brain TRM Formation and Function

Glial Cell Expression of PD-L1

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About

Reactive glia promote development of CD103⁺CD69⁺ CD8⁺ T‐cells through programmed cell death‐ligand 1 (PD‐L1)

Reactive glia promote development of CD103⁺CD69⁺ CD8⁺ T‐cells through programmed cell death‐ligand 1 (PD‐L1)