scholarly journals Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses

2020 ◽  
Vol 217 (8) ◽  
Author(s):  
Jun Siong Low ◽  
Yagmur Farsakoglu ◽  
Maria Carolina Amezcua Vesely ◽  
Esen Sefik ◽  
Joseph B. Kelly ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Functional Responses ◽  
Memory Cd8 T Cells ◽  
Cell Reactivation ◽  
Gfp Reporter ◽  
Antigen Presenting ◽  
Resident Memory T Cells

CD8+ tissue-resident memory T cells (TRM cells) are poised at the portals of infection and provide long-term protective immunity. Despite their critical roles, the precise mechanics governing TRM cell reactivation in situ are unknown. Using a TCR-transgenic Nur77-GFP reporter to distinguish “antigen-specific” from “bystander” reactivation, we demonstrate that lung CD8+ TRM cells are reactivated more quickly, yet less efficiently, than their counterparts in the draining LNs (TLN cells). Global profiling of reactivated memory T cells revealed tissue-defined and temporally regulated recall response programs. Unlike the reactivation of CD8+ TLN cells, which is strictly dependent on CD11c+XCR1+ APCs, numerous antigen-presenting partners, both hematopoietic and non-hematopoietic, were sufficient to reactivate lung CD8+ TRM cells, but the quality of TRM cell functional responses depended on the identity of the APCs. Together, this work uncovers fundamental differences in the activation kinetics, mechanics, and effector responses between CD8+ memory T cells in peripheral vs. lymphoid organs, revealing a novel tissue-specific paradigm for the reactivation of memory CD8+ T cells.

scholarly journals CXCR6 regulates localization of tissue-resident memory CD8 T cells to the airways

2019 ◽  
Vol 216 (12) ◽  
pp. 2748-2762 ◽  
Author(s):  
Alexander N. Wein ◽  
Sean R. McMaster ◽  
Shiki Takamura ◽  
Paul R. Dunbar ◽  
Emily K. Cartwright ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Memory T Cells ◽  
Respiratory Pathogens ◽  
First Line ◽  
Memory Cd8 T Cells ◽  
Effector Functions ◽  
Signaling Axis ◽  
Resident Memory T Cells

Resident memory T cells (TRM cells) are an important first-line defense against respiratory pathogens, but the unique contributions of lung TRM cell populations to protective immunity and the factors that govern their localization to different compartments of the lung are not well understood. Here, we show that airway and interstitial TRM cells have distinct effector functions and that CXCR6 controls the partitioning of TRM cells within the lung by recruiting CD8 TRM cells to the airways. The absence of CXCR6 significantly decreases airway CD8 TRM cells due to altered trafficking of CXCR6−/− cells within the lung, and not decreased survival in the airways. CXCL16, the ligand for CXCR6, is localized primarily at the respiratory epithelium, and mice lacking CXCL16 also had decreased CD8 TRM cells in the airways. Finally, blocking CXCL16 inhibited the steady-state maintenance of airway TRM cells. Thus, the CXCR6/CXCL16 signaling axis controls the localization of TRM cells to different compartments of the lung and maintains airway TRM cells.

Circulating memory CD8 + T cells are limited in forming CD103 + tissue‐resident memory T cells at mucosal sites after reinfection

2020 ◽  
Author(s):  
Felix M. Behr ◽  
Ammarina Beumer‐Chuwonpad ◽  
Natasja A. M. Kragten ◽  
Thomas H. Wesselink ◽  
Regina Stark ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
Memory Cd8 T Cells ◽  
Resident Memory T Cells

scholarly journals Therapeutic activation of virus-specific resident memory T cells within the glioblastoma microenvironment

2021 ◽  
Author(s):  
Jianfang Ning ◽  
Noah Gavil ◽  
Shaoping Wu ◽  
Sathi Wijeyesinghe ◽  
Eyob Weyu ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Activation ◽  
Memory T Cells ◽  
Standard Of Care ◽  
Free Virus ◽  
Memory Cd8 T Cells ◽  
Specific Memory ◽  
Care Surgery ◽  
Tumor Types ◽  
Resident Memory T Cells

Glioblastoma multiforme (GBM) is among the most aggressive, treatment resistant cancers, and despite standard of care surgery, radiation and chemotherapy, is invariably fatal. GBM is marked by local and systemic immunosuppression, contributing to resistance to existing immunotherapies that have had success in other tumor types. Memory T cells specific for previous infections reside in tissues throughout the host and these tissue resident memory T cells (TRM) are capable of rapid and potent immune activation. Here, we show that virus-specific memory CD8+ T cells expressing tissue resident markers populate mouse and human glioblastoma microenvironment. Reactivating virus-specific TRM through intra-tumoral delivery of adjuvant-free virus-derived peptide triggered local immune activation. This delivery translated to anti-neoplastic effects, which improved survival in a murine glioblastoma model. Our results indicate that virus-specific TRM are a significant part of the glioblastoma immune microenvironment and can be leveraged to promote anti-tumoral immunity.

Skin-resident memory CD8+ T cells trigger a state of tissue-wide pathogen alert

Science ◽  
2014 ◽  
Vol 346 (6205) ◽  
pp. 101-105 ◽  
Author(s):  
Silvia Ariotti ◽  
Marc A. Hogenbirk ◽  
Feline E. Dijkgraaf ◽  
Lindy L. Visser ◽  
Mirjam E. Hoekstra ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
Mouse Skin ◽  
Memory Cd8 T Cells ◽  
Vaccination Strategies ◽  
Rapid Control ◽  
Pathogen Entry ◽  
Specific Tissue ◽  
Resident Memory T Cells

After an infection, pathogen-specific tissue-resident memory T cells (TRM cells) persist in nonlymphoid tissues to provide rapid control upon reinfection, and vaccination strategies that create TRM cell pools at sites of pathogen entry are therefore attractive. However, it is not well understood how TRM cells provide such pathogen protection. Here, we demonstrate that activated TRM cells in mouse skin profoundly alter the local tissue environment by inducing a number of broadly active antiviral and antibacterial genes. This “pathogen alert” allows skin TRM cells to protect against an antigenically unrelated virus. These data describe a mechanism by which tissue-resident memory CD8+ T cells protect previously infected sites that is rapid, amplifies the activation of a small number of cells into an organ-wide response, and has the capacity to control escape variants.

scholarly journals Resident Memory T Cells and Their Effect on Cancer

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 562
Author(s):  
Daniel J. Craig ◽  
Justin F. Creeden ◽  
Katelyn R. Einloth ◽  
Cassidy E. Gillman ◽  
Laura Stanbery ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
Cell Transformation ◽  
Cell Phenotype ◽  
Long Term Memory ◽  
Potential Applications ◽  
Resident Memory T Cells ◽  
Cancer Immunosurveillance

Resident memory T (TRM) cells are a unique subset of CD8+ T cells that are present within certain tissues and do not recirculate through the blood. Long term memory establishment and maintenance are dependent on tissue population of memory T cells. They are characterized by dual CD69/CD103 positivity, and play a role in both response to viral infection and local cancer immunosurveillance. Human TRM cells demonstrate the increased expression of adhesion molecules to facilitate tissue retention, have reduced proliferation and produce both regulatory and immune responsive cytokines. TRM cell phenotype is often characterized by a distinct expression profile driven by Runx3, Blimp1, and Hobit transcription factors. The accumulation of TRM cells in tumors is associated with increased survival and response to immunotherapies, including anti-PD-1 and anti-CTLA-4. In this review, we explore potential mechanisms of TRM cell transformation and maintenance, as well as potential applications for the use of TRM cells in both the development of supportive therapies and establishing more accurate prognoses.

scholarly journals Human CD4+CD103+ cutaneous resident memory T cells are found in the circulation of healthy individuals

2019 ◽  
Vol 4 (37) ◽  
pp. eaav8995 ◽  
Author(s):  
Maria M. Klicznik ◽  
Peter A. Morawski ◽  
Barbara Höllbacher ◽  
Suraj R. Varkhande ◽  
Samantha J. Motley ◽  
...  
Keyword(s):  
T Cells ◽  
Human Skin ◽  
Memory T Cells ◽  
Xenograft Model ◽  
T Cell Memory ◽  
Explant Cultures ◽  
Distant Tissue ◽  
Resident Memory T Cells ◽  
Skin Xenograft

Tissue-resident memory T cells (TRM) persist locally in nonlymphoid tissues where they provide frontline defense against recurring insults. TRM at barrier surfaces express the markers CD103 and/or CD69, which function to retain them in epithelial tissues. In humans, neither the long-term migratory behavior of TRM nor their ability to reenter the circulation and potentially migrate to distant tissue sites has been investigated. Using tissue explant cultures, we found that CD4+CD69+CD103+ TRM in human skin can down-regulate CD69 and exit the tissue. In addition, we identified a skin-tropic CD4+CD69−CD103+ population in human lymph and blood that is transcriptionally, functionally, and clonally related to the CD4+CD69+CD103+ TRM population in the skin. Using a skin xenograft model, we confirmed that a fraction of the human cutaneous CD4+CD103+ TRM population can reenter circulation and migrate to secondary human skin sites where they reassume a TRM phenotype. Thus, our data challenge current concepts regarding the strict tissue compartmentalization of CD4+ T cell memory in humans.

scholarly journals Tissue-Resident Memory T Cells in Skin Diseases: A Systematic Review

2021 ◽  
Vol 22 (16) ◽  
pp. 9004
Author(s):  
Thomas Emmanuel ◽  
Josephine Mistegård ◽  
Anne Bregnhøj ◽  
Claus Johansen ◽  
Lars Iversen
Keyword(s):  
T Cells ◽  
Skin Diseases ◽  
Memory T Cells ◽  
Future Research ◽  
Inclusion Criteria ◽  
Local Skin ◽  
Resident Memory T Cells ◽  
Infectious Skin Diseases

In health, the non-recirculating nature and long-term persistence of tissue-resident memory T cells (TRMs) in tissues protects against invading pathogens. In disease, pathogenic TRMs contribute to the recurring traits of many skin diseases. We aimed to conduct a systematic literature review on the current understanding of the role of TRMs in skin diseases and identify gaps as well as future research paths. EMBASE, PubMed, SCOPUS, Web of Science, Clinicaltrials.gov and WHO Trials Registry were searched systematically for relevant studies from their inception to October 2020. Included studies were reviewed independently by two authors. This study was conducted in accordance with the PRISMA-S guidelines. This protocol was registered with the PROSPERO database (ref: CRD42020206416). We identified 96 studies meeting the inclusion criteria. TRMs have mostly been investigated in murine skin and in relation to infectious skin diseases. Pathogenic TRMs have been characterized in various skin diseases including psoriasis, vitiligo and cutaneous T-cell lymphoma. Studies are needed to discover biomarkers that may delineate TRMs poised for pathogenic activity in skin diseases and establish to which extent TRMs are contingent on the local skin microenvironment. Additionally, future studies may investigate the effects of current treatments on the persistence of pathogenic TRMs in human skin.

scholarly journals Tissue-resident memory T cells in tumor immunity and immunotherapy

2021 ◽  
Vol 218 (4) ◽  
Author(s):  
Karolina Okła ◽  
Donna L. Farber ◽  
Weiping Zou
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Tumor Immunity ◽  
Memory T Cells ◽  
Protective Role ◽  
Peripheral Tissues ◽  
Patients With Cancer ◽  
Favorable Clinical Outcome ◽  
Resident Memory T Cells

Tissue-resident memory T cells (TRM) represent a heterogeneous T cell population with the functionality of both effector and memory T cells. TRM express residence gene signatures. This feature allows them to traffic to, reside in, and potentially patrol peripheral tissues, thereby enforcing an efficient long-term immune-protective role. Recent studies have revealed TRM involvement in tumor immune responses. TRM tumor infiltration correlates with enhanced response to current immunotherapy and is often associated with favorable clinical outcome in patients with cancer. Thus, targeting TRM may lead to enhanced cancer immunotherapy efficacy. Here, we review and discuss recent advances on the nature of TRM in the context of tumor immunity and immunotherapy.

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