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

2018 ◽  
Author(s):  
M. M. Klicznik ◽  
P. A. Morawski ◽  
B. Höllbacher ◽  
S. R. Varkhande ◽  
S. Motley ◽  
...  
Keyword(s):  
T Cells ◽  
Human Skin ◽  
Healthy Subjects ◽  
Memory T Cells ◽  
Xenograft Model ◽  
Lymphoid Tissues ◽  
Distant Tissue ◽  
Resident Memory T Cells ◽  
Skin Xenograft

AbstractTissue-resident memory T cells (TRM) persist locally in non-lymphoid tissues where they provide front-line 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 re-enter the circulation and potentially migrate to distant tissue sites have been investigated. Using tissue explant cultures, we found that CD4+CD69+CD103+ TRM in human skin can downregulate CD69 and exit the tissue.Additionally, 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 re-enter circulation, and migrate to secondary human skin sites where they re-assume a TRM phenotype. Thus, our data challenge current concepts regarding the strict tissue compartmentalization of CD4+ T cell memory in humans.One Sentence SummaryHuman CD4+CD103+ cutaneous resident memory T cells are found in the circulation of healthy subjects, and these cells can seed distant skin sites.

scholarly journals CCR8 Expression Defines Tissue-Resident Memory T Cells in Human Skin

2018 ◽  
pp. ji1701377 ◽  
Author(s):  
Michelle L. McCully ◽  
Kristin Ladell ◽  
Robert Andrews ◽  
Rhiannon E. Jones ◽  
Kelly L. Miners ◽  
...  
Keyword(s):  
T Cells ◽  
Human Skin ◽  
Memory T Cells ◽  
Resident Memory T Cells

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 Circulating CD4+ memory T cells give rise to a CD69+ resident memory T cell population in non-inflamed human skin

2018 ◽  
Author(s):  
Maria M Klicznik ◽  
Ariane Benedetti ◽  
Angelika Stoecklinger ◽  
Daniel J Campbell ◽  
Iris K Gratz
Keyword(s):  
T Cells ◽  
Candida Albicans ◽  
T Cell ◽  
Human Skin ◽  
Cell Population ◽  
Memory T Cells ◽  
Humanized Mouse Model ◽  
Normal Human Skin ◽  
Memory T Cell ◽  
Resident Memory T Cells

The blood of human adults contains a pool of circulating CD4+ memory T cells and normal human skin contains a CD4+CD69+ memory T cell population that produce IL17 in response to Candida albicans. Here we studied the generation of CD4+CD69+ memory T cells in human skin from a pool of circulating CD4+ memory T cells. Using adoptive transfer of human PBMC into a skin-humanized mouse model we discovered the generation of CD4+CD69+ resident memory T cells in human skin in absence of infection or inflammation. These CD4+CD69+ resident memory T cells were activated and displayed heightened effector function in response to Candida albicans. These studies demonstrate that a CD4+CD69+ T cell population can be established in human skin from a pool of circulating CD4+ memory T cells in absence of infection/inflammation. The described process might be a novel way to spread antigen-specific immunity at large barrier sites even in absence of infection or inflammation.

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.

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 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 Longevity and replenishment of human liver-resident memory T cells and mononuclear phagocytes

2020 ◽  
Vol 217 (9) ◽  
Author(s):  
Laura J. Pallett ◽  
Alice R. Burton ◽  
Oliver E. Amin ◽  
Sergio Rodriguez-Tajes ◽  
Amit A. Patel ◽  
...  
Keyword(s):  
T Cells ◽  
Kupffer Cells ◽  
Human Liver ◽  
Memory T Cells ◽  
Mononuclear Phagocytes ◽  
Term Retention ◽  
Donor Cells ◽  
Long Term Retention ◽  
Resident Memory T Cells

The human liver contains specialized subsets of mononuclear phagocytes (MNPs) and T cells, but whether these have definitive features of tissue residence (long-term retention, lack of egress) and/or can be replenished from the circulation remains unclear. Here we addressed these questions using HLA-mismatched liver allografts to discriminate the liver-resident (donor) from the infiltrating (recipient) immune composition. Allografts were rapidly infiltrated by recipient leukocytes, which recapitulated the liver myeloid and lymphoid composition, and underwent partial reprogramming with acquisition of CD68/CD206 on MNPs and CD69/CD103 on T cells. The small residual pool of donor cells persisting in allografts for over a decade contained CX3CR1hi/CD163hi/CD206hi Kupffer cells (KCs) and CXCR3hi tissue-resident memory T cells (TRM). CD8+ TRM were found in the local lymph nodes but were not detected egressing into the hepatic vein. Our findings inform organ transplantation and hepatic immunotherapy, revealing remarkably long-lived populations of KCs and TRM in human liver, which can be additionally supplemented by their circulating counterparts.

Sign in / Sign up

Export Citation Format

Share Document