scholarly journals CD4+ Resident Memory T Cells Mediate Long-Term Local Skin Immune Memory of Contact Hypersensitivity in BALB/c Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
Akihiko Murata ◽  
Shin-Ichi Hayashi
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Contact Hypersensitivity ◽  
Immune Memory ◽  
Local Skin ◽  
Resident Memory T Cells

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 Id3 and Bcl6 Promote the Development of Long-Term Immune Memory Induced by Tuberculosis Subunit Vaccine

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 126
Author(s):  
Jiangyuan Han ◽  
Yanlin Ma ◽  
Lan Ma ◽  
Daquan Tan ◽  
Hongxia Niu ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Subunit Vaccine ◽  
Memory T Cells ◽  
Transcriptional Factors ◽  
Immune Memory ◽  
Proliferative Potential ◽  
Adeno Associated Virus ◽  
Adjuvant Effects

Long-lived memory cell formation and maintenance are usually regulated by cytokines and transcriptional factors. Adjuvant effects of IL-7 have been studied in the vaccines of influenza and other pathogens. However, few studies investigated the adjuvant effects of cytokines and transcriptional factors in prolonging the immune memory induced by a tuberculosis (TB) subunit vaccine. To address this research gap, mice were treated with the Mycobacterium tuberculosis (M. tuberculosis) subunit vaccine Mtb10.4-HspX (MH) plus ESAT6-Ag85B-MPT64<190–198>-Mtb8.4-Rv2626c (LT70), together with adeno-associated virus-mediated IL-7 or lentivirus-mediated transcriptional factor Id3, Bcl6, Bach2, and Blimp1 at 0, 2, and 4 weeks, respectively. Immune responses induced by the vaccine were examined at 25 weeks after last immunization. The results showed that adeno-associated virus-mediated IL-7 allowed the TB subunit vaccine to induce the formation of long-lived memory T cells. Meanwhile, IL-7 increased the expression of Id3, Bcl6, and bach2—the three key transcription factors for the generation of long-lived memory T cells. The adjuvant effects of transcriptional factors, together with TB fusion protein MH/LT70 vaccination, showed that both Bcl6 and Id3 increased the production of antigen-specific antibodies and long-lived memory T cells, characterized by high proliferative potential of antigen-specific CD4+ and CD8+ T cells, and IFN-γ secretion in CD4+ and CD8+ T cells, respectively, after re-exposure to the same antigen. Overall, our study suggests that IL-7 and transcriptional factors Id3 and Bcl6 help the TB subunit vaccine to induce long-term immune memory, which contributes to providing immune protection against M. tuberculosis infection.

scholarly journals Mobilization of tissue-resident memory CD4+ T lymphocytes and their contribution to a systemic secondary immune reaction

2020 ◽  
Author(s):  
Carla Cendón ◽  
Weijie Du ◽  
Pawel Durek ◽  
Tobias Alexander ◽  
Lindsay Serene ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Immune Responses ◽  
Immune Reaction ◽  
Memory T Cells ◽  
Time Window ◽  
Immune Memory ◽  
Resident Memory T Cells ◽  
Memory T Lymphocytes

AbstractWhile it is generally accepted that tissue-resident memory T lymphocytes protect host tissues from secondary immune challenges, it is unclear whether, and if so, how they contribute to systemic secondary immune responses. Here we show that in human individuals with an established immune memory to measles, mumps and rubella viruses, when challenged with the measles-mumps-rubella (MMR) vaccine again, tissue-resident memory CD4+ T cells are mobilized into the blood within 16 to 48 hours after vaccination. These cells then leave the blood again, and apparently contribute to the systemic secondary immune reaction, as is evident from the representation of mobilized T cell receptor Vβ clonotypes among newly generated circulating memory T lymphocytes, from day 7 onwards. Mobilization of the tissue-resident memory T cells is cognate, in that memory T lymphocytes recognizing other antigens, e.g. tetanus toxin, are not mobilized, unless they cross-react with the vaccine. These data originally demonstrate the essential contribution of tissue-resident memory T cells to secondary systemic immune responses, confirming that immunological memories to systemic pathogens are maintained (also) by tissue-resident memory T cells. In practical terms, the present work defines day 1 to 2 after antigenic challenge as a time window to assess the entire immunological T cell memory for a certain pathogen, including mobilized tissue-resident memory T cells, and its correlates of effectivity.Capsule summaryThe study demonstrates the rapid and cognate mobilization of tissue-resident memory CD4+ T cells into the blood upon antigenic rechallenge, and their contribution to secondary systemic immune responses.

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 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 Distinct Time Effects of Vaccination on Long-Term Proliferative and IFN-γ–producing T Cell Memory to Smallpox in Humans

2004 ◽  
Vol 199 (11) ◽  
pp. 1585-1593 ◽  
Author(s):  
Behazine Combadiere ◽  
Alexandre Boissonnas ◽  
Guislaine Carcelain ◽  
Evelyne Lefranc ◽  
Assia Samri ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Immune Memory ◽  
Effector Memory ◽  
Long Term Memory ◽  
Smallpox Virus ◽  
Effector Memory Cells ◽  
Ifn Γ

Residual immunity to the smallpox virus raises key questions about the persistence of long-term immune memory in the absence of antigen, since vaccination ended in 1980. IFN-γ–producing effector–memory and proliferative memory T cells were compared in 79 vaccinees 13–25 yr after their last immunization and in unvaccinated individuals. Only 20% of the vaccinees displayed both immediate IFN-γ–producing effector–memory responses and proliferative memory responses at 6 d; 52.5% showed only proliferative responses; and 27.5% had no detectable vaccinia-specific responses at all. Both responses were mediated by CD4 and CD8 T cells. The vaccinia-specific IFN-γ–producing cells were composed mainly of CD4Pos CD45RANeg CD11aHi CD27Pos and CCR7Neg T cells. Their frequency was low but could be expanded in vitro within 7 d. Time since first immunization affected their persistence: they vanished 45 yr after priming, but proliferative responses remained detectable. The number of recalls did not affect the persistence of residual effector–memory T cells. Programmed revaccination boosted both IFN-γ and proliferative responses within 2 mo of recall, even in vaccinees with previously undetectable residual effector–memory cells. Such long-term maintenance of vaccinia-specific immune memory in the absence of smallpox virus modifies our understanding of the mechanism of persistence of long-term memory to poxviruses and challenges vaccination strategies.

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