scholarly journals White adipose tissue inflammation is not attenuated by short-term calorie restriction in obese humans

2019 ◽  
Author(s):  
Julia Sbierski-Kind ◽  
Knut Mai ◽  
Jonas Kath ◽  
Anke Jurisch ◽  
Mathias Streitz ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Immune Cell ◽  
Memory T Cells ◽  
Cell Receptor ◽  
Effector Memory ◽  
Short Term ◽  
Effector Memory T Cells ◽  
Cytokine Levels

AbstractObesity is a growing global health problem due to its association with chronic low-grade inflammation contributing to metabolic complications. Multiple studies indicate that white adipose tissue (WAT) inflammation can promote type 2 diabetes. However, the function and regulation of both innate and adaptive immune cells in human WAT under conditions of obesity and calorie restriction (CR) is not fully understood yet. Using a randomized interventional design, we investigated postmenopausal obese women who either underwent CR for three months followed by a 4 weeks phase of weight maintenance or had to maintain a stable weight over the whole study period. A comprehensive immune phenotyping protocol was conducted using validated multiparameter flow cytometry analysis in blood and subcutaneous WAT (SAT) (n=21). The T cell receptor repertoire was analyzed by next generation sequencing (n=20) and cytokine levels were determined in SAT (n=22). Metabolic parameters were determined by hyperinsulinemic-euglycemic clamp and then correlated to immune cell subsets. We found that insulin resistance (IR) correlates significantly with a shift towards the memory T cell compartment in SAT. Among various T cell subsets, predominantly CD8+ effector memory T cells were associated with obesity-related IR. Interestingly, T cell receptor analysis revealed a diverse repertoire in SAT arguing against an antigen-driven intra-SAT expansion of effector memory T cells. Surprisingly, neither inflammatory cytokine levels nor leucocyte subpopulations were significantly altered upon CR. Our findings demonstrate the accumulation of effector memory T cells in obese SAT contributing to chronic inflammation. The long-standing effect of obesity-induced changes in SAT was demonstrated by preserved immune cell composition after short-term CR induced weight loss.

scholarly journals Balancing Inflammation and Central Nervous System Homeostasis: T Cell Receptor Signaling in Antiviral Brain TRM Formation and Function

2021 ◽  
Vol 11 ◽  
Author(s):  
Colleen S. Netherby-Winslow ◽  
Katelyn N. Ayers ◽  
Aron E. Lukacher
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Memory T Cells ◽  
Infectious Agent ◽  
Cell Receptor ◽  
Effector Memory ◽  
Tcr Signaling ◽  
And Function ◽  
Barrier Tissues

Tissue-resident memory (TRM) CD8 T cells provide early frontline defense against regional pathogen reencounter. CD8 TRM are predominantly parked in nonlymphoid tissues and do not circulate. In addition to this anatomic difference, TRM are transcriptionally and phenotypically distinct from central-memory T cells (TCM) and effector-memory T cells (TEM). Moreover, TRM differ phenotypically, functionally, and transcriptionally across barrier tissues (e.g., gastrointestinal tract, respiratory tract, urogenital tract, and skin) and in non-barrier organs (e.g., brain, liver, kidney). In the brain, TRM are governed by a contextual milieu that balances TRM activation and preservation of essential post-mitotic neurons. Factors contributing to the development and maintenance of brain TRM, of which T cell receptor (TCR) signal strength and duration is a central determinant, vary depending on the infectious agent and modulation of TCR signaling by inhibitory markers that quell potentially pathogenic inflammation. This review will explore our current understanding of the context-dependent factors that drive the acquisition of brain (b)TRM phenotype and function, and discuss the contribution of TRM to promoting protective immune responses in situ while maintaining tissue homeostasis.

scholarly journals Chronic Plasmodium chabaudi Infection Generates CD4 Memory T Cells with Increased T Cell Receptor Sensitivity but Poor Secondary Expansion and Increased Apoptosis

2016 ◽  
Vol 85 (3) ◽  
Author(s):  
Michael M. Opata ◽  
Robin Stephens
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Chronic Infection ◽  
Malaria Infection ◽  
Memory T Cells ◽  
Cell Receptor ◽  
Blood Stage ◽  
Effector Memory ◽  
Plasmodium Chabaudi

ABSTRACT Exposure to blood-stage malaria infection is often persistent, leading to generation of CD4 effector and effector memory T cells that contribute to protection. We showed previously that chronic exposure to blood-stage Plasmodium chabaudi offers the best protection from parasitemia and pathology in reinfection cases, correlating with an increase in Th1 cells. Although much is known about the features of resting or exhausted memory T cells (Tmem), little is known about the functional capacities of chronically stimulated but protective T cells. To determine the functional capacity of CD4 T cells generated by chronic infection upon reexposure to parasite, we compared their responses to known features of classical Tmem. The numbers of cytokine-producing T cells increased following infection in the polyclonal populations, suggesting an increase in pathogen-specific T cells. Malaria antigen-specific B5 T cell receptor (TCR) transgenic (Tg) T cells from chronic infection proliferated on reinfection and were highly sensitive to TCR stimulation without costimulation, as shown for Tmem in acute stimulations. However, B5 Tmem did not accumulate more than naive B5 T cells in vivo or in vitro and became apoptotic. Failure to accumulate was partly the result of chronic stimulation, since eliminating persistent parasites before reinfection slightly increased the accumulation of B5 Tg T cells upon reinfection. The levels of specific gamma interferon-positive, interleukin-10-positive T cells, which protect animals from pathology, increased after malaria infection. These data demonstrate that although chronic infection generates a protective T cell population with increased TCR sensitivity and cytokine production, they do not reexpand upon reexposure due to increased apoptosis.

scholarly journals Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Takahiko Miyama ◽  
Takakazu Kawase ◽  
Kazutaka Kitaura ◽  
Ren Chishaki ◽  
Masashi Shibata ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Memory T Cells ◽  
Cell Receptor

scholarly journals P083 Characterisation of T-cell receptor repertoire patterns of circulating a4b7 positive memory T cells in ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S176-S177
Author(s):  
A Gamliel ◽  
L Werner ◽  
N Salamon ◽  
M Pinsker ◽  
B Weiss ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Memory T Cells ◽  
Cell Receptor ◽  
Control Subjects ◽  
Receptor Repertoire ◽  
Negative Memory ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

Abstract Background Memory T cells play an important role in mediating inflammatory responses in IBD. The integrin a4b7 is highly expressed on activated T cells, and is thought to direct homing of lymphocytes to the intestine, following its binding to MADCAM-1 expressed exclusively on intestinal endothelial cells. Since UC is characterised by oligoclonal expansion of specific T-cell clonotypes, we hypothesised that circulating memory T cells with gut-homing potential would exhibit unique T-cell receptor repertoire features. Methods Peripheral blood mononuclear cells were collected from 5 control subjects and 6 pediatric patients with active UC. Following CD3 MACS sorting cells were FACS sorted into a4b7 positive and a4b7 negative CD3+CD45RO+ memory T cells. DNA was Isolated from each subset and subjected to next-generation sequencing of the TCRB. This high-throughput platform employs massive parallel sequencing to process millions of rearranged T-cell receptor (TCR) products simultaneously, and permits an in-depth analysis of individual TCRs at the nucleotide level. Comparisons of different indices of diversity, CDR3 length and clonal biochemical characteristics were performed between a4b7 positive and a4b7 negative populations for each subject, and between controls and UC patients. Results PBMCs were isolated from active UC patients during endoscopic assessment. Four patients had a Mayo endoscopic score of 2, and two patients had a score of 1. Only one patient was treated with an immunosuppressive medication (azathioprine), and five out of six patients were treated with 5ASAs. Percentages of memory T cells (43.8 ± 12.3% vs. 32.2 ± 13.1%, p = 0.17) and a4b7 positive T cells (33.6 ± 15.7% vs. 36.0 ± 17.6%, p = 0.81) were comparable between controls and UC patients. Interestingly, a4b7 positive memory T cells displayed a polyclonal distribution, in both control subjects and in UC patients, without expansion of specific clones. Different indices of diversity, including shanon’s H, clonality index and entropy, were similar among controls and patients, both for a4b7 positive and a4b7 negative populations. Finally, clonal overlap between a4b7 positive and a4b7 negative memory T cells, for each subject was high, ranging between 30–50% for controls and 27–48% for UC patients. Conclusion a4b7 expressing memory T cells exhibited a polyclonal repertoire in both control subjects and patients with active UC, with high rates of overlap with a4b7 negative memory T cells. Our study, along with additional recent reports, challenge the dogma of the importance of a4b7 expression for T-cell migration to the gut, and may suggest that vedolizumab’s suppresses intestinal inflammation by blocking the trafficking of innate immune subsets.

Flt3 ligand augmentation of T cell mitogenesis and expansion of type 1 effector/memory T cells

2002 ◽  
Vol 2 (7) ◽  
pp. 925-940 ◽  
Author(s):  
R Lee Mosley ◽  
Prahlad Parajuli ◽  
Vladimir Pisarev ◽  
Jennifer Chavez ◽  
Amy Meeks ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Effector Memory ◽  
Flt3 Ligand ◽  
Effector Memory T Cells

Tolerogenic dendritic cells inhibit antiphospholipid syndrome derived effector/memory CD4+ T cell response to β2GPI

2011 ◽  
Vol 71 (1) ◽  
pp. 120-128 ◽  
Author(s):  
Honorio Torres-Aguilar ◽  
Miri Blank ◽  
Shaye Kivity ◽  
Mudi Misgav ◽  
Jacob Luboshitz ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Proliferative Response ◽  
Memory T Cells ◽  
Tolerance Induction ◽  
Effector Memory ◽  
Effector Memory T Cells ◽  
Tolerogenic Dendritic Cells ◽  
Specific Tolerance

ObjectivesThe importance of β2-glycoprotein I (β2GPI)-specific CD4+ T cells in the development of pathogenic processes in patients with antiphospholipid syndrome (APS) and APS mouse models is well established. Therefore, our objective is to manipulate the β2GPI specific CD4+ T cells using tolerogenic dendritic cells (tDCs) to induce tolerance. We aim to evaluate the capability of tDCs to induce antigen-specific tolerance in effector/memory T cells from patients with APS and to elucidate the involved mechanism.MethodsDCs and tDCs were produced from patients with APS peripheral-blood-monocytes, using specific cytokines. β2GPI-specific tolerance induction was investigated by coculturing control DC (cDC) or tDC, β2GPI-loaded, with autologous effector/memory T cells, evaluating the proliferative response, phenotype, cytokines secretion, viability and regulatory T cells.ResultsHuman monocyte-derived DCs treated with interleukin (IL)-10 and transforming growth factor β-1 (10/TGF-DC) induced β2GPI-specific-unresponsiveness in effector/memory CD4+ T cells (46.5%±26.0 less proliferation) in 16 of 20 analysed patients with APS, without affecting the proliferative response to an unrelated candidin. In five analysed patients, 10/TGF-DC-stimulated T cells acquired an IL-2lowinterferon γlowIL-10high cytokine profile, with just a propensity to express higher numbers of Foxp3+CTLA-4+ cells, but with an evident suppressive ability. In four of 10 analysed patients, 10/TGF-DC-stimulated T cell hyporesponsiveness could not be reverted and showed higher percentages of late apoptosis, p<0.02.ConclusionsThe inherent tolerance induction resistance of activated T cells present during the development of autoimmune diseases has delayed the application of tDC as an alternative therapy. This study highlights the 10/TGF-DC feasibility to induce antigen-specific unresponsiveness in autoreactive T cells generated in patients with APS by inducing apoptosis or T cells with regulatory abilities.

Unique gene expression program of human germinal center T helper cells

Blood ◽  
2004 ◽  
Vol 104 (7) ◽  
pp. 1952-1960 ◽  
Author(s):  
Chang H. Kim ◽  
Hyung W. Lim ◽  
Jong R. Kim ◽  
Lusijah Rott ◽  
Peter Hillsamer ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Germinal Center ◽  
Memory T Cells ◽  
Effector Memory ◽  
T Helper ◽  
Th Cells ◽  
Effector Memory T Cells ◽  
Expression Program

Abstract Gene expression profiling was used to compare the gene expression patterns of human germinal center (GC) T helper (Th) cells with other CD4+ T-cell subsets (naive, central, and effector memory T cells). GC-Th cells, specifically localized in germinal centers to help B cells, are distantly related to central and effector memory T cells in global gene expression profiles. GC-Th cells displayed substantial differences in mRNA for adhesion molecules, chemoattractant receptors, and cytokines compared with other populations. Distinct expression of transcriptional factors by GC-Th cells is consistent with the hypothesis that they may be different from other T cells in cell lineage. Interestingly, CXCL13, a critical chemokine for B-cell entry to lymphoid follicles, is one of the most highly up-regulated genes in GC-Th cells. GC-Th cells (but not other T cells) produce and secrete large amounts of functional CXCL13 upon T-cell receptor activation, a process that is dependent on costimulation, requires translation and transcription, and is dramatically enhanced by activation in the presence of GC-B cells. This study revealed for the first time the unique gene expression program of GC-Th cells.

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