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 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 TGF-[beta]-dependent Lymphoid Tissue Residency of Stem-like T cells Limits the Response to Tumor Vaccine

2021 ◽  
Author(s):  
Guo Li ◽  
Liwen Wang ◽  
Chaoyu Ma ◽  
Wei Liao ◽  
Yong Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
Tumor Vaccine ◽  
Tumor Control ◽  
Lymphoid Tissues ◽  
Dependent Manner ◽  
Multiple Tumor ◽  
Draining Lymph Node ◽  
Resident Memory T Cells

Stem-like CD8+ T cells represent the key subset responding to multiple tumor immunotherapies, including tumor vaccination. However, the signals that control the differentiation of stem-like T cells are not entirely known. Most previous investigations on stem-like T cells are focused on tumor infiltrating T cells (TIL). The behavior of stem-like T cells in other tissues remains to be elucidated. Tissue-resident memory T cells (TRM) are often defined as a non-circulating T cell population residing in non-lymphoid tissues. TILs carrying TRM features are associated with better tumor control. Here, we found that stem-like CD8+ T cells differentiated into TRMs in a TGF-β and tumor antigen dependent manner almost exclusively in tumor draining lymph node (TDLN). TDLN-resident stem-like T cells were negatively associated with the response to tumor vaccine. In other words, after tumor vaccine, TDLN stem-like T cells transiently lost TRM features, differentiated into migratory effectors and exerted tumor control.

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 The relationship between CD4+ follicular helper T cells and CD8+ resident memory T cells: sisters or distant cousins?

2020 ◽  
Vol 32 (9) ◽  
pp. 583-587 ◽  
Author(s):  
Changwei Peng ◽  
Stephen C Jameson
Keyword(s):  
T Cells ◽  
Immune System ◽  
Protective Immunity ◽  
Memory T Cells ◽  
Helper T Cells ◽  
Lymphoid Tissues ◽  
Follicular Helper T Cells ◽  
Follicular Helper ◽  
Resident Memory T Cells ◽  
The Relationship

Abstract Independent studies over the last decade have characterized the properties of non-circulating CD8+ ‘resident’ memory T cells (TRM), which offer barrier protective immunity in non-lymphoid tissues and CD4+ follicular helper T cells (TFH), which mediate B-cell help in lymphoid sites. Despite their very different biological roles in the immune system, intriguing parallels have been noted between the trafficking properties and differentiation cues of these populations, parallels which have only sharpened with recent findings. In this review, we explore the features that underlie these similarities and discuss whether these indicate meaningful homologies in the development of CD8+ TRM and CD4+ TFH or reflect resemblances which are only ‘skin-deep’.

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.

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