History of child maltreatment and telomere length in immune cell subsets: Associations with stress- and attachment-related hormones

2017 ◽  
Vol 30 (2) ◽  
pp. 539-551 ◽  
Author(s):  
Christina Boeck ◽  
Sabrina Krause ◽  
Alexander Karabatsiakis ◽  
Katharina Schury ◽  
Harald Gündel ◽  
...  
Keyword(s):  
T Cells ◽  
Child Maltreatment ◽  
Telomere Length ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Cytotoxic T Cells ◽  
Peripheral Blood Mononuclear ◽  
Protective Function ◽  
Biological Stress ◽  
Immune Cell Subsets

AbstractExperiencing maltreatment during childhood can have long-lasting consequences for both mental and physical health. Immune cell telomere length (TL) shortening might be one link between child maltreatment (CM) experiences and adverse health outcomes later in life. While the stress hormone cortisol has been associated with TL attrition, the attachment-related hormone oxytocin may promote resilience. In 15 mothers with and 15 age- and body mass index-matched mothers without CM, we assessed TL in peripheral blood mononuclear cells and selected immune cell subsets (monocytes, naive, and memory cytotoxic T cells) by quantitative fluorescence in situ hybridization, as well as peripheral cortisol and oxytocin levels. Memory cytotoxic T cells showed significantly shorter TL in association with CM, whereas TL in monocytes and naive cytotoxic T cells did not significantly differ between the two groups. Across both groups, cortisol was negatively associated with TL, while oxytocin was positively associated with TL in memory cytotoxic T cells. These results indicate that long-lived memory cytotoxic T cells are most affected by the increased biological stress state associated with CM. Keeping in mind the correlational and preliminary nature of the results, the data suggest that cortisol may have a damaging and oxytocin a protective function on TL.

scholarly journals Impaired Anti-Tumor T cell Response in Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 627 ◽  
Author(s):  
Nada Chaoul ◽  
Serena Mancarella ◽  
Luigi Lupo ◽  
Gianluigi Giannelli ◽  
Francesco Dituri
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
T Cell Response ◽  
Effector Memory ◽  
Peripheral Blood Mononuclear ◽  
Immune Cell Subsets ◽  
Memory Cd4 T Cells

Different subsets of lymphocytes have the capacity to promote or counteract the progression of solid cancers, including hepatocellular carcinoma (HCC). Therefore, to determine the infiltrative ability and functional status of major immune cell subtypes into tumor may lead to novel insights from the perspective of immunotherapy. After obtaining single cell suspensions from freshly collected specimens of HCC tumor, along with paired peritumor tissues and peripheral blood mononuclear cells (PBMCs) from 14 patients, we flow-cytometrically identified and quantified the relative frequencies of lymphocyte subsets within the tissues of origin. We found that the recruitment in the tumor of cytotoxic cells, namely the terminally differentiated CD4+ and CD8+ T cells (TEFF), is impaired, whereas the effector memory CD4+ T cells (TEM) are more attracted in this site. Concerning the other subsets, the frequency of NK CD56hi and NKT CD56hi cells infiltration in the tumor is increased, whereas that of NKT CD56low is reduced. Although CD4+ and CD8+ T cells settled in the tumor show a higher degree of activation than the circulating counterpart, they occur with a more exhausted phenotype. Overall, these data demonstrate the prevalently immunosuppressive nature of HCC microenvironment, and prompt us to search for strategies to enhance the activity of anti-tumor immune cell subsets.

scholarly journals Endogenous retrovirus-encoded Syncytin-2 contributes to exosome-mediated immunosuppression of T cells†

2019 ◽  
Author(s):  
Adjimon G Lokossou ◽  
Caroline Toudic ◽  
Phuong Trang Nguyen ◽  
Xavier Elisseeff ◽  
Amandine Vargas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Map Kinases ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Endogenous Retrovirus ◽  
Jurkat Cells ◽  
Peripheral Blood Mononuclear ◽  
Interfering Rna

Abstract Modulation of the activation status of immune cell populations during pregnancy depends on placental villous cytotrophoblast (VCT) cells and the syncytiotrophoblast (STB). Failure in the establishment of this immunoregulatory function leads to pregnancy complications. Our laboratory has been studying Syncytin-2 (Syn-2), an endogenous retroviral protein expressed in placenta and on the surface of placental exosomes. This protein plays an important role not only in STB formation through its fusogenic properties, but also through its immunosuppressive domain (ISD). Considering that Syn-2 expression is importantly reduced in preeclamptic placentas, we were interested in addressing its possible immunoregulatory effects on T cells. Activated Jurkat T cells and peripheral blood mononuclear cells (PBMCs) were treated with monomeric or dimerized version of a control or a Syn-2 ISD peptide. Change in phosphorylation levels of ERK1/2 MAP kinases was selectively noted in Jurkat cells treated with the dimerized ISD peptide. Upon incubation with the dimerized Syn-2 ISD peptide, significant reduction in Th1 cytokine production was further demonstrated by ELISA and Human Th1/Th2 Panel Multi-Analyte Flow Assay. To determine if exosome-associated Syn-2 could also be immunosuppressive placental exosomes were incubated with activated Jurkat and PBMCs. Quantification of Th1 cytokines in the supernatants revealed severe reduction in T cell activation. Interestingly, exosomes from Syn-2-silenced VCT incubated with PBMCs were less suppressive when compared with exosome derived from VCT transfected with control small interfering RNA (siRNA). Our results suggest that Syn-2 is an important immune regulator both locally and systemically, via its association with placental exosomes.

scholarly journals Acetate correlates with disability and immune response in multiple sclerosis

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10220 ◽  
Author(s):  
Silvia Pérez-Pérez ◽  
María Inmaculada Domínguez-Mozo ◽  
Aitana Alonso-Gómez ◽  
Silvia Medina ◽  
Noelia Villarrubia ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Short Chain Fatty Acids ◽  
Liquid Chromatography Mass Spectrometry ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Disability Status

Background Gut microbiota has been related to multiple sclerosis (MS) etiopathogenesis. Short-chain fatty acids (SCFA) are compounds derived from microbial metabolism that have a role in gut-brain axis. Objectives To analyse SCFA levels in plasma of MS patients and healthy donors (HD), and the possible link between these levels and both clinical data and immune cell populations. Methods Ninety-five MS patients and 54 HD were recruited. Patients were selected according to their score in the Expanded Disability Status Scale (EDSS) (49 EDSS ≤ 1.5, 46 EDSS ≥ 5.0). SCFA were studied in plasma samples by liquid chromatography-mass spectrometry. Peripheral blood mononuclear cells were studied by flow cytometry. Gender, age, treatments, EDSS and Multiple Sclerosis Severity Score (MSSS) were evaluated at the recruitment. Results Plasma acetate levels were higher in patients than in HD (p = 0.003). Patients with EDSS ≥ 5.0 had higher acetate levels than those with EDSS≤ 1.5 (p = 0.029), and HD (p = 2.97e–4). Acetate levels correlated with EDSS (r = 0.387; p = 1.08e–4) and MSSS (r = 0.265; p = 0.011). In untreated MS patients, acetate levels correlated inversely with CD4+ naïve T cells (r =  − 0.550, p = 0.001) and directly with CD8+ IL-17+ cells (r = 0.557; p = 0.001). Conclusions Plasma acetate levels are higher in MS patients than in HD. In MS there exists a correlation between plasma acetate levels, EDSS and increased IL-17+ T cells. Future studies will elucidate the role of SCFA in the disease.

scholarly journals Preliminary evidence of reductive stress in human cytotoxic T cells following exercise

2018 ◽  
Vol 125 (2) ◽  
pp. 586-595 ◽  
Author(s):  
Alex J. Wadley ◽  
Adrian Holliday ◽  
Rhys G. Morgan ◽  
Kate J. Heesom ◽  
Sarah Aldred ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Exercise ◽  
Mononuclear Cells ◽  
Cytotoxic T Cells ◽  
Preliminary Evidence ◽  
Tolerance Test ◽  
Oxygen Intake ◽  
Peripheral Blood Mononuclear ◽  
Reductive Stress ◽  
Thiol Redox

This study investigated immunophenotypic differences in intracellular thiol redox state of peripheral blood mononuclear cells (PBMCs) isolated from trained [ n = 9, means ± SD: age 28 ± 5 yr; (body mass index) BMI 23.2 ± 2.6 kg/m2; V̇o2max (maximal oxygen intake)56.9 ± 6.1 ml·kg−1·min−1] and recreationally active (RA, n = 11, means ± SD: age 27 ± 6 yr; BMI 24.2 ± 3.7 kg/m2; V̇o2max 45.1 ± 6.4 ml·kg−1·min−1) participants before and after a maximal aerobic exercise tolerance test. Blood samples were taken before (Pre), during (sample acquired at 70% maximum heart rate), immediately after (Post + 0), and 15 min postexercise (Post + 15). PBMCs were isolated, and reduced thiol analysis [fluorescein-5 maleimide (F5M)] by immunophenotype [cluster of differentiation (CD)3+, CD4+, and CD8+] was performed using flow cytometry. A significant increase in cellular F5M fluorescence was observed in CD3+ T cells at Post + 0, with changes driven to a greater extent by CD8+ T cells (fold change in both groups CD4: +2.3, CD8: +2.8; P < 0.05). Further analysis revealed a population of highly reduced CD8+ T cells (CD8+T-reduced+) that significantly increased from Pre to Post + 0 in RA participants only (RA: +272 cell/µl, P < 0.05). To understand these results further, CD8+T-reduced+ and CD8+T-reduced− cells were analyzed for immunophenotype in response to the same exercise protocol ( n = 6, means ± SD: age 24 ± 5 yr; BMI 25.7 ± 4.1 kg·m−2; V̇o2max 41.33 ± 7.63 ml·kg−1·min−1). CD8+T-reduced+ had significantly less lymphoid homing potential (chemokine receptor type 7) Post + 0 compared with Pre. This study is the first, to our knowledge, to demonstrate that lymphocyte populations become more reductive in response to acute exercise. NEW & NOTEWORTHY The study presented provides the first evidence to suggest that cytotoxic T cells become transiently reductive in healthy individuals following a single bout of cycling. Detection of these cells was enabled via the use of a flow cytometric assay that incorporates the thiol reactive probe fluorescein-5 maleimide. Using this method, transient reductive stress in viable T cells is permissible and provides the basis for further research in the area of exercise immunology.

scholarly journals Expansion of HIV-specific CD4+ and CD8+ T cells by dendritic cells transfected with mRNA encoding cytoplasm- or lysosome-targeted Nef

Blood ◽  
2006 ◽  
Vol 107 (5) ◽  
pp. 1963-1969 ◽  
Author(s):  
Daniel G. Kavanagh ◽  
Daniel E. Kaufmann ◽  
Sherzana Sunderji ◽  
Nicole Frahm ◽  
Sylvie Le Gall ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Cytotoxic T Cells ◽  
T Cell Response ◽  
Peripheral Blood Mononuclear ◽  
T Cell Lines

Transfection with synthetic mRNA is a safe and efficient method of delivering antigens to dendritic cells for immunotherapy. Targeting antigens to the lysosome can sometimes enhance the CD4+ T-cell response. We transfected antigen-presenting cells (APCs) with mRNA encoding Gag-p24 and cytoplasmic, lysosomal, and secreted forms of Nef. Antigen-specific cytotoxic T cells were able to lyse the majority of transfected targets, indicating that transfection was efficient. Transfection of APCs with a Nef construct bearing lysosomal targeting signals produced rapid and prolonged antigen presentation to CD4+ and CD8+ T cells. Polyclonal CD4+ and CD8+ T-cell lines recognizing multiple distinct epitopes were expanded by coculture of transfected dendritic cells with peripheral blood mononuclear cells from viremic and aviremic HIV-infected subjects. Importantly, lysosome-targeted antigen drove a significantly greater expansion of Nef-specific CD4+ T cells than cytoplasmic antigen. The frequency of recognition of CD8 but not CD4 epitopes by mRNA-expanded T cells was inversely proportional to sequence entropy and was similar to ex vivo responses from a large chronic cohort. Thus human dendritic cells transfected with mRNA encoding lysosome-targeted HIV antigen can expand a broad, polyclonal repertoire of antiviral T cells, offering a promising approach to HIV immunotherapy.

scholarly journals The differential immune responses to COVID-19 in peripheral and lung revealed by single-cell RNA sequencing

2020 ◽  
Author(s):  
Gang Xu ◽  
Furong Qi ◽  
Hanjie Li ◽  
Qianting Yang ◽  
Haiyan Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Close Association ◽  
Suppressor Cells ◽  
T Cell Subsets ◽  
Peripheral Blood Mononuclear ◽  
Peripheral T Cells

Understanding the mechanism that leads to immune dysfunction induced by SARS-CoV2 virus is crucial to develop treatment for severe COVID-19. Here, using single cell RNA-seq, we characterized the peripheral blood mononuclear cells (PBMC) from uninfected controls and COVID-19 patients, and cells in paired broncho-alveolar lavage fluid (BALF). We found a close association of decreased dendritic cells (DC) and increased monocytes resembling myeloid-derived suppressor cells (MDSC) which correlated with lymphopenia and inflammation in the blood of severe COVID-19 patients. Those MDSC-like monocytes were immune-paralyzed. In contrast, monocyte-macrophages in BALFs of COVID-19 patients produced massive amounts of cytokines and chemokines, but secreted little interferons. The frequencies of peripheral T cells and NK cells were significantly decreased in severe COVID-19 patients, especially for innate-like T and various CD8+ T cell subsets, compared to health controls. In contrast, the proportions of various activated CD4+ T cell subsets, including Th1, Th2 and Th17-like cells were increased and more clonally expanded in severe COVID-19 patients. Patients' peripheral T cells showed no sign of exhaustion or augmented cell death, whereas T cells in BALFs produced higher levels of IFNG, TNF, CCL4 and CCL5 etc. Paired TCR tracking indicated abundant recruitment of peripheral T cells to the patients' lung. Together, this study comprehensively depicts how the immune cell landscape is perturbed in severe COVID-19.

scholarly journals IL-12 Gene Electrotransfer Triggers a Change in Immune Response within Mouse Tumors

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 498 ◽  
Author(s):  
Guilan Shi ◽  
Chelsea Edelblute ◽  
Sezgi Arpag ◽  
Cathryn Lundberg ◽  
Richard Heller
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Immune Memory ◽  
Control Group ◽  
Gene Electrotransfer ◽  
Cell Content ◽  
Peripheral Blood Mononuclear

Metastatic melanoma is an aggressive skin cancer with a relatively low survival rate. Immune-based therapies have shown promise in the treatment of melanoma, but overall complete response rates are still low. Previous studies have demonstrated the potential of plasmid IL-12 (pIL-12) delivered by gene electrotransfer (GET) to be an effective immunotherapy for melanoma. However, events occurring in the tumor microenvironment following delivery have not been delineated. Therefore, utilizing a B16F10 mouse melanoma model, we evaluated changes in the tumor microenvironment following delivery of pIL-12 using different GET parameters or injection of plasmid alone. The results revealed a unique immune cell composition after intratumoral injection of pIL-12 GET. The number of immune memory cells was markedly increased in pIL-12 GET melanoma groups compared to control group. This was validated using flow cytometry to analyze peripheral blood mononuclear cells as well as delineating immune cell content using immunohistochemistry. Significant differences in multiple cell types were observed, including CD8+ T cells, regulatory T cells and myeloid cells, which were induced to mount a CD8+PD1− T cells immune response. Taken together, these findings suggest a basic understanding of the sequence of immune activity following pIL-12 GET and also illuminates that adjuvant immunotherapy can have a positive influence on the host immune response to cancer.

scholarly journals In Vitro Responsiveness of γδ T Cells fromMycobacterium bovis-Infected Cattle to Mycobacterial Antigens: Predominant Involvement of WC1+Cells

2001 ◽  
Vol 69 (1) ◽  
pp. 89-96 ◽  
Author(s):  
Allister J. Smyth ◽  
Michael D. Welsh ◽  
R. Martyn Girvin ◽  
John M. Pollock
Keyword(s):  
T Cells ◽  
Diagnostic Tests ◽  
Protective Immunity ◽  
Cellular Proliferation ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Γδ T Cells ◽  
Peripheral Blood Mononuclear ◽  
Cell Functions

ABSTRACT It is generally accepted that protective immunity against tuberculosis is generated through the cell-mediated immune (CMI) system, and a greater understanding of such responses is required if better vaccines and diagnostic tests are to be developed. γδ T cells form a major proportion of the peripheral blood mononuclear cells (PBMC) in the ruminant system and, considering data from other species, may have a significant role in CMI responses in bovine tuberculosis. This study compared the in vitro responses of αβ and γδ T cells from Mycobacterium bovis-infected and uninfected cattle. The results showed that, following 24 h of culture of PBMC withM. bovis-derived antigens, the majority of γδ T cells from infected animals became highly activated (upregulation of interleukin-2R), while a lower proportion of the αβ T-cell population showed activation. Similar responses were evident to a lesser degree in uninfected animals. Study of the kinetics of this response showed that γδ T cells remained significantly activated for at least 7 days in culture, while activation of αβ T cells declined during that period. Subsequent analysis revealed that the majority of activated γδ T cells expressed WC1, a 215-kDa surface molecule which is not expressed on human or murine γδ T cells. Furthermore, in comparison with what was found for CD4+ T cells, M. bovis antigen was found to induce strong cellular proliferation but relatively little gamma interferon release by purified WC1+ γδ T cells. Overall, while the role of these cells in protective immunity remains unclear, their highly activated status in response to M. bovis suggests an important role in antimycobacterial immunity, and the ability of γδ T cells to influence other immune cell functions remains to be elucidated, particularly in relation to CMI-based diagnostic tests.

Sign in / Sign up

Export Citation Format

Share Document