1675-P: Adipocyte Adaptive Immune Cell Function and Exhaustion Contribute to the Drop in Adipose Tissue (AT) Regulatory T-Cells (Tregs) in Human Obesity

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1675-P
Author(s):  
DAVID BRADLEY ◽  
ALECIA M. BLASZCZAK ◽  
ALAN SMITH ◽  
ANAHITA D. JALILVAND ◽  
VALERIE P. WRIGHT ◽  
...  
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
Regulatory T Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Immune Cell Function ◽  
Human Obesity ◽  
Adaptive Immune ◽  
Adaptive Immune Cell

scholarly journals IL-2–dependent tuning of NK cell sensitivity for target cells is controlled by regulatory T cells

2013 ◽  
Vol 210 (6) ◽  
pp. 1167-1178 ◽  
Author(s):  
Georg Gasteiger ◽  
Saskia Hemmers ◽  
Matthew A. Firth ◽  
Audrey Le Floc’h ◽  
Morgan Huse ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Nk Cells ◽  
Immune Cell ◽  
Nk Cell ◽  
Adaptive Immune System ◽  
Target Cells ◽  
Cell Reactivity ◽  
Adaptive Immune ◽  
Missing Self

The emergence of the adaptive immune system took a toll in the form of pathologies mediated by self-reactive cells. Regulatory T cells (T reg cells) exert a critical brake on responses of T and B lymphocytes to self- and foreign antigens. Here, we asked whether T reg cells are required to restrain NK cells, the third lymphocyte lineage, whose features combine innate and adaptive immune cell properties. Although depletion of T reg cells led to systemic fatal autoimmunity, NK cell tolerance and reactivity to strong activating self- and non-self–ligands remained largely intact. In contrast, missing-self responses were increased in the absence of T reg cells as the result of heightened IL-2 availability. We found that IL-2 rapidly boosted the capacity of NK cells to productively engage target cells and enabled NK cell responses to weak stimulation. Our results suggest that IL-2–dependent adaptive-innate lymphocyte cross talk tunes NK cell reactivity and that T reg cells restrain NK cell cytotoxicity by limiting the availability of IL-2.

scholarly journals Analysis of adaptive immune cell populations and phenotypes in the patients infected by SARS-CoV-2

2020 ◽  
Author(s):  
Xiaofeng Yang ◽  
Tongxin Dai ◽  
Xiaobo Zhou ◽  
Hongbo Qian ◽  
Rui Guo ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Immune Cell ◽  
Age Groups ◽  
Cell Populations ◽  
Adaptive Immune ◽  
Adaptive Immune Cell ◽  
Cell Percentage ◽  
Enhanced Expression ◽  
Functional Features

AbstractCoronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, has rapidly spread to most of countries in the world, threatening the health and lives of many people. Unfortunately, information regarding the immunological characteristics in COVID-19 patients remains limited. Here we collected the blood samples from 18 healthy donors (HD) and 38 COVID-19 patients to analyze changes in the adaptive immune cell populations and phenotypes. In comparison to HD, the lymphocyte percentage was slightly decreased, the percentages of CD4 and CD8 T cells in lymphocytes are similar, whereas B cell percentage increased in COVID-19 patients. T cells, especially CD8 T cells, showed an enhanced expression of late activation marker CD25 and exhaustion marker PD-1. Importantly, SARS-CoV-2 induced an increased percentage of T follicular helpher (Tfh)- and germinal center B-like (GCB-like) cells in the blood. However, the parameters in COVD-19 patients remained unchanged across various age groups. Therefore, we demonstrated that the T and B cells can be activated normally and exhibit functional features. These data provide a clue that the adaptive immunity in most people could be primed to induce a significant immune response against SARS-CoV-2 infection upon receiving standard medical care.

Role of Regulatory T Cells in Infection and Vaccination During Early Infancy

2018 ◽  
Vol 24 (30) ◽  
pp. 3495-3505
Author(s):  
Samanta C. Funes ◽  
Miguel A. Mansilla ◽  
Gisela Canedo-Marroquín ◽  
Margarita K. Lay ◽  
Claudia A. Riedel ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Active Role ◽  
Treg Cells ◽  
Health Goals ◽  
Inhibitory Mechanisms ◽  
Neonates And Infants

Reducing infant mortality due to infectious diseases is one of the most important public health goals worldwide. Several approaches have been implemented to reach this goal and vaccination has been an effective strategy for reducing infant and newborn mortality. However, the immunological features of neonates and infants represent a significant barrier to the effectiveness of vaccination. Since regulatory T cells (Treg cells) are known to play an active role in contributing to various mechanisms of suppression of the immune cell function. It has been proposed that these immune cells could decrease the immunogenicity of vaccines administered in newborns and infants. In this article, we discuss the various types of Treg cells, along with their suppressing and inhibitory mechanisms, which are used by these cells in the context of infectious and immunization processes in newborns and infants.

scholarly journals Human Tissue-Resident Memory T Cells in the Maternal–Fetal Interface. Lost Soldiers or Special Forces?

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2699
Author(s):  
Caitlin S. DeJong ◽  
Nicholas J. Maurice ◽  
Stephen A. McCartney ◽  
Martin Prlic
Keyword(s):  
T Cells ◽  
Immune System ◽  
Cell Function ◽  
Immune Cell ◽  
Memory T Cells ◽  
Critical Role ◽  
Immune Cell Function ◽  
Histocompatibility Complex ◽  
Resident Memory T Cells ◽  
Maternal Fetal Interface

The immune system plays a critical role during pregnancy, but the specific mechanisms and immune cell function needed to support pregnancy remain incompletely understood. Despite decades of research efforts, it is still unclear how the immune system maintains tolerance of fetal-derived tissues, which include most cells of the placenta and of course the fetus itself, without forfeiting the ability to protect against harmful infections. T cells recognize antigen in the context of major histocompatibility complex (MHC) encoded proteins, but classical MHC class I and II expression are diminished in fetal-derived cells. Can T cells present at the maternal–fetal interface (MFI) protect these cells from infection? Here we review what is known in regard to tissue-resident memory T (Trm) cells at the MFI. We mainly focus on how Trm cells can contribute to protection in the context of the unique features of the MFI, such as limited MHC expression as well as the temporary nature of the MFI, that are not found in other tissues.

scholarly journals Regulatory T cells in acute and chronic kidney diseases

2018 ◽  
Vol 314 (5) ◽  
pp. F679-F698 ◽  
Author(s):  
Rahul Sharma ◽  
Gilbert R. Kinsey
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cell Activation ◽  
Cell Function ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Kidney Diseases ◽  
Peripheral Tolerance ◽  
Autoimmune And Inflammatory Diseases

Foxp3-expressing CD4+ regulatory T cells (Tregs) make up one subset of the helper T cells (Th) and are one of the major mechanisms of peripheral tolerance. Tregs prevent abnormal activation of the immune system throughout the lifespan, thus protecting from autoimmune and inflammatory diseases. Recent studies have elucidated the role of Tregs beyond autoimmunity. Tregs play important functions in controlling not only innate and adaptive immune cell activation, but also regulate nonimmune cell function during insults and injury. Inflammation contributes to a multitude of acute and chronic diseases affecting the kidneys. This review examines the role of Tregs in pathogenesis of renal inflammatory diseases and explores the approaches for enhancing Tregs for prevention and therapy of renal inflammation.

scholarly journals Phosphoinositide 3-kinase δ (PI3Kδ) in respiratory disease

2018 ◽  
Vol 46 (2) ◽  
pp. 361-369 ◽  
Author(s):  
Clare A. Stokes ◽  
Alison M. Condliffe
Keyword(s):  
Airway Inflammation ◽  
Cell Function ◽  
Immune Cell ◽  
Respiratory Infections ◽  
Therapeutic Option ◽  
Neutrophil Function ◽  
Histone Deacetylase 2 ◽  
Cell Functions ◽  
Adaptive Immune ◽  
Adaptive Immune Cell

Defining features of chronic airway diseases include abnormal and persistent inflammatory processes, impaired airway epithelial integrity and function, and increased susceptibility to recurrent respiratory infections. Phosphoinositide 3-kinases (PI3K) are lipid kinases, which contribute to multiple physiological and pathological processes within the airway, with abnormal PI3K signalling contributing to the pathogenesis of several respiratory diseases. Consequently, the potential benefit of targeting PI3K isoforms has received considerable attention, being viewed as a viable therapeutic option in inflammatory and infectious lung disorders. The class I PI3K isoform, PI3Kδ (Phosphoinositide 3-kinases δ) is of particular interest given its multiple roles in modulating innate and adaptive immune cell functions, airway inflammation and corticosteroid sensitivity. In this mini-review, we explore the role of PI3Kδ in airway inflammation and infection, focusing on oxidative stress, ER stress, histone deacetylase 2 and neutrophil function. We also describe the importance of PI3Kδ in adaptive immune cell function, as highlighted by the recently described Activated PI3K Delta Syndrome, and draw attention to some of the potential clinical applications and benefits of targeting this molecule.

scholarly journals CD16ahigh NK cell infiltration and spatial relationships with T cells and macrophages can predict improved progression-free survival in high grade ovarian cancer

2021 ◽  
Author(s):  
Sarah Nersesian ◽  
Stacey N Lee ◽  
Stephanie Grantham ◽  
Liliane Meunier ◽  
Laudine Communal ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Immune Cell ◽  
Nk Cell ◽  
Cell Subset ◽  
Progression Free Survival ◽  
High Grade ◽  
Free Survival ◽  
Adaptive Immune ◽  
Adaptive Immune Cell

Background: High grade serous cancer (HGSC) remains a highly fatal malignancy with less than 50% of patients surviving 5 years after diagnosis. Despite its high mutational burden, HGSC is relatively refractory to checkpoint immunotherapy, suggesting that additional features of the cancer and its interactions with the immune system remain to be understood. Natural killer (NK) cells may contribute to HGSC control, but the role(s) of this population or its subsets in this disease are poorly understood. Methods: We used a TMA containing duplicate treatment-naive tumors from 1145 patients with HGSC and a custom staining panel to simultaneously measure macrophages, T cells and NK cells, separating NK cells based on CD16a expression. Using pathologist-validated digital pathology, machine learning, computational analysis and Pearsons correlations, we quantitated infiltrating immune cell density, co-infiltration and co-localization with spatial resolution to tumor region. We compared the prognostic value of innate, general, and adaptive immune cell neighborhoods to define characteristics of HGSC tumors predictive for progression-free survival and used flow cytometry to define additional features of the CD16adim NK cell subset. Results: NK cells were observed in >95% of tumor cores. Intrastromal localization of CD16alow and CD16ahigh NK cells was associated with shorter and longer progression-free survival, respectively. CD16ahigh NK cells most frequently co-localized with T cells and macrophages; their proximity was termed an adaptive neighborhood. We find that tumors with more area represented by adaptive immune cell neighborhoods corresponded to superior progression free survival. In contrast, CD16alow NK cells did not co-infiltrate with other immune cell types, and expressed the ectonucleotidases, CD39 and CD73, which have been previously associated with poor prognosis in patients with HGSC. Conclusions: Progression-free survival for patients with HGSC may be predicted by the subset of NK cells within the tumor infiltrate (i.e. CD16ahigh vs. CD16alow). NK cell subtypes were associated predictable co-infiltrating and co-localizing leukocyte subsets, suggesting that their presence and activity may influence, or be influenced by the tumor microenvironment. Our data suggest that immunotherapeutic strategies for HGSC should consider the constitution of NK cell subsets and may benefit from mobilizing and activating CD16high NK cells.

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