Tissue-Resident Memory T Cells Mediate Immune Homeostasis in the Human Pancreas through the PD-1/PD-L1 Pathway

Weisberg, Stuart P.; Carpenter, Dustin; Chait, Michael; Dogra, Pranay; Gartrell, Robyn D.; Chen, Andrew X.; Campbell, Sammy C.; Liu, Wei; Saraf, Pooja; Snyder, Mark E.; Kubota, Masaru; Danzl, Nichole; Schrope, Beth; Rabadán, Raúl; Saenger, Yvonne M.; Chen, Xiaojuan; Farber, Donna L.

doi:10.1016/j.celrep.2019.11.056

Cited by 73 publications

(78 citation statements)

References 86 publications

(131 reference statements)

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“…The primary critique of studies performed using peripheral blood is that the relationship between tissue-infiltrating and circulating autoreactive CD8 T cells is poorly defined. Many studies of postmortem samples of pancreata revealed the dominant presence of CD8 T cells in donors with T1D and healthy pancreas (18)(19)(20). Using HLA class-I tetramers, Coppieters et al provided the first proof that CD8 T cells reactive against IGRP 265-273 , IA-2 797-805 , and PPI 15-24 could be found in situ in the islets from individuals with recent-onset and long-standing T1D (21).…”

Section: The Presence Of Autoreactive Cd8 T Cells In the Target Organmentioning

confidence: 99%

New Insights Into the Role of Autoreactive CD8 T Cells and Cytokines in Human Type 1 Diabetes

2021

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Since the establishment of the network for pancreatic organ donors with diabetes (nPOD), we have gained unprecedented insight into the pathology of human type 1 diabetes. Many of the pre-existing “dogmas”, mostly derived from studies of animal models and sometimes limited human samples, have to be revised now. For example, we have learned that autoreactive CD8 T cells are present even in healthy individuals within the exocrine pancreas. Furthermore, their “attraction” to islets probably relies on beta-cell intrinsic events, such as the over-expression of MHC class I and resulting presentation of autoantigens such as (prepro)insulin. In addition, we are discovering other signs of beta-cell dysfunction, possibly at least in part due to stress, such as the over-expression of certain cytokines. This review summarizes the latest developments focusing on cytokines and autoreactive CD8 T cells in human type 1 diabetes pathogenesis.

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Section: The Presence Of Autoreactive Cd8 T Cells In the Target Organmentioning

confidence: 99%

New Insights Into the Role of Autoreactive CD8 T Cells and Cytokines in Human Type 1 Diabetes

2021

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“…Although the upregulation of PD-1 in cancer and chronic infection is associated with T cell exhaustion, the physiological role of PD-1 is not negative by definition. For example, T RM cells mediate immune homeostasis in the human pancreas through the PD-1/PD-L1 pathway [ 90 ]. In addition, the expression of inhibitory receptors, including PD-1 and Tim-3, may prevent T RM -mediated immunopathology in chronic inflammatory diseases [ 91 ].…”

Section: Functional Heterogeneity and Therapeutic Targetingmentioning

confidence: 99%

Functional Heterogeneity and Therapeutic Targeting of Tissue-Resident Memory T Cells

Gracht

Behr

Arens

2021

Cells

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Tissue-resident memory T (TRM) cells mediate potent local innate and adaptive immune responses and provide long-lasting protective immunity. TRM cells localize to many different tissues, including barrier tissues, and play a crucial role in protection against infectious and malignant disease. The formation and maintenance of TRM cells are influenced by numerous factors, including inflammation, antigen triggering, and tissue-specific cues. Emerging evidence suggests that these signals also contribute to heterogeneity within the TRM cell compartment. Here, we review the phenotypic and functional heterogeneity of CD8+ TRM cells at different tissue sites and the molecular determinants defining CD8+ TRM cell subsets. We further discuss the possibilities of targeting the unique cell surface molecules, cytokine and chemokine receptors, transcription factors, and metabolic features of TRM cells for therapeutic purposes. Their crucial role in immune protection and their location at the frontlines of the immune defense make TRM cells attractive therapeutic targets. A better understanding of the possibilities to selectively modulate TRM cell populations may thus improve vaccination and immunotherapeutic strategies employing these potent immune cells.

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“…Likewise, human T RM cells express CXCR6 across multiple tissues [48]. The molecules PD-1 and CD101 are also commonly expressed by T RM cells from different tissues [45,48,67,68]. In contrast, most T RM cells are negative for the chemokine receptor CX3CR1 [6], which is found on some circulating memory T cells in mice and humans [13,48].…”

Section: T Rm Cell Development and General Featuresmentioning

confidence: 99%

Resident Memory T Cells and Their Role within the Liver

Ghilas

Valencia-Hernandez

Enders

et al. 2020

IJMS

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Immunological memory is fundamental to maintain immunity against re-invading pathogens. It is the basis for prolonged protection induced by vaccines and can be mediated by humoral or cellular responses—the latter largely mediated by T cells. Memory T cells belong to different subsets with specialized functions and distributions within the body. They can be broadly separated into circulating memory cells, which pace the entire body through the lymphatics and blood, and tissue-resident memory T (TRM) cells, which are constrained to peripheral tissues. Retained in the tissues where they form, TRM cells provide a frontline defense against reinfection. Here, we review this population of cells with specific attention to the liver, where TRM cells have been found to protect against infections, in particular those by Plasmodium species that cause malaria.

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Tissue-Resident Memory T Cells Mediate Immune Homeostasis in the Human Pancreas through the PD-1/PD-L1 Pathway

Cited by 73 publications

References 86 publications

New Insights Into the Role of Autoreactive CD8 T Cells and Cytokines in Human Type 1 Diabetes

New Insights Into the Role of Autoreactive CD8 T Cells and Cytokines in Human Type 1 Diabetes

Functional Heterogeneity and Therapeutic Targeting of Tissue-Resident Memory T Cells

Resident Memory T Cells and Their Role within the Liver

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