scholarly journals Involvement of Different CD4+T Cell Subsets Producing Granzyme B in the Immune Response toLeishmania majorAntigens

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Ikbel Naouar ◽  
Thouraya Boussoffara ◽  
Melika Ben Ahmed ◽  
Nabil Belhaj Hmida ◽  
Adel Gharbi ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Leishmania Major ◽  
Mononuclear Cells ◽  
Cytotoxic T Cells ◽  
Granzyme B ◽  
T Cell Subsets ◽  
Peripheral Blood Mononuclear ◽  
Effector Cells

The nature of effector cells and the potential immunogenicity ofLeishmania majorexcreted/secreted proteins (LmES) were evaluated using peripheral blood mononuclear cells (PBMCs) from healed zoonotic cutaneous leishmaniasis individuals (HZCL) and healthy controls (HC). First, we found that PBMCs from HZCL individuals proliferate and produce high levels of IFN-γand granzyme B (GrB), used as a marker of activated cytotoxic T cells, in response to the parasite antigens. IFN-γis produced by CD4+T cells, but unexpectedly GrB is also produced by CD4+T cells in response to stimulation withLmES, which were found to be as effective as solubleLeishmaniaantigens to induce proliferation and cytokine production by PBMCs from immune individuals. To address the question of regulatory T cell (Tregs) involvement, the frequency of circulating Tregs was assessed and found to be higher in HZCL individuals compared to that of HC. Furthermore, both CD4+CD25+and CD4+CD25−T cells, purified from HZCL individuals, produced IFN-γand GrB when stimulated withLmES. Additional experiments showed thatCD4+CD25+CD127dim/-Tregs were involved in GrB production. Collectively, our data indicate thatLmES are immunogenic in humans and emphasize the involvement of CD4+T cells including activated and regulatory T cells in the immune response against parasite antigens.

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 Activation of natural regulatory T cells by IgG Fc–derived peptide “Tregitopes”

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3303-3311 ◽  
Author(s):  
Anne S. De Groot ◽  
Leonard Moise ◽  
Julie A. McMurry ◽  
Erik Wambre ◽  
Laurence Van Overtvelt ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Regulatory T Cell ◽  
Mononuclear Cells ◽  
T Cell Epitopes ◽  
Peripheral Blood Mononuclear ◽  
Murine Homologue

Abstract We have identified at least 2 highly promiscuous major histocompatibility complex class II T-cell epitopes in the Fc fragment of IgG that are capable of specifically activating CD4+CD25HiFoxP3+ natural regulatory T cells (nTRegs). Coincubation of these regulatory T-cell epitopes or “Tregitopes” and antigens with peripheral blood mononuclear cells led to a suppression of effector cytokine secretion, reduced proliferation of effector T cells, and caused an increase in cell surface markers associated with TRegs such as FoxP3. In vivo administration of the murine homologue of the Fc region Tregitope resulted in suppression of immune response to a known immunogen. These data suggest that one mechanism for the immunosuppressive activity of IgG, such as with IVIG, may be related to the activity of regulatory T cells. In this model, regulatory T-cell epitopes in IgG activate a subset of nTRegs that tips the resulting immune response toward tolerance rather than immunogenicity.

scholarly journals Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts

2020 ◽  
Author(s):  
Pedro Henrique Ferreira Marçal ◽  
Rafael Silva Gama ◽  
Lorena Bruna de Oliveira Pereira ◽  
Olindo Assis Martins Filho ◽  
Roberta Olmo Pinheiro ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Clinical Status ◽  
T Cell Subsets ◽  
Diagnostic Tools ◽  
Peripheral Blood Mononuclear ◽  
Household Contacts ◽  
Leprosy Patients

Abstract Background: Leprosy is a chronic infectious disease classified into two subgroups for therapeutic purposes: paucibacillary (PB) and multibacillary (MB), closely related to the host immune responses. In this context it is noteworthy looking for immunological biomarkers applicable as complementary diagnostic tools as well as a laboratorial strategy to detect subclinical leprosy in household contacts. Methods: The main goal of the present study was to characterize the global cytokine signatures of CD4+ and CD8+ T-cells from leprosy patients with distinct clinical forms and their respective household contacts (HHC) upon in vitro antigen-specific stimuli. Short-term culture of peripheral blood mononuclear cells was done. After incubation, cells were harvested and prepared for surface and intracytoplasmic cytokine staining Results: The cytokine signature analysis demonstrated that leprosy patients presented a polyfunctional profile of T-cells subsets, with increased frequency of IFN-g+ T-cell subsets along with IL-10+ and IL-4+ from CD4+ T-cells. Moreover, L(PB) displayed a polyfunctional profile characterized by enhanced percentage of IFN-g+, IL-10+ and IL-4+ produced by most T-cell subsets, as compared to L(MB) that presented a more restricted cytokine functional profile mediated by IL-10+ and IL-4+ T-cells with minor contribution of IFN-g produced by CD4+ T-cells. Noteworthy was that HHC(MB) exhibited enhanced frequency of IFN-g+ T-cells, contrasting with HHC(PB) that presented a cytokine profile limited to IL-10 and IL-4. Conclusions: Together, our findings provide additional immunological features associated with leprosy and household contacts. These data provide evidence that biomarkers of immune response can be useful complementary diagnostic/prognostic tools as well as insights that household contacts may present subclinical infection.

scholarly journals Regulation of T Cells in Cancer by Nitric Oxide

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2655
Author(s):  
Inesa Navasardyan ◽  
Benjamin Bonavida
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Suppressor Cells ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Target Cells ◽  
Effector Cells ◽  
Cell Functions

The T cell-mediated immune response is primarily involved in the fight against infectious diseases and cancer and its underlying mechanisms are complex. The anti-tumor T cell response is regulated by various T cell subsets and other cells and tissues in the tumor microenvironment (TME). Various mechanisms are involved in the regulation of these various effector cells. One mechanism is the iNOS/.NO that has been reported to be intimately involved in the regulation and differentiation of the various cells that regulate the anti-tumor CD8 T cells. Both endogenous and exogenous .NO are implicated in this regulation. Importantly, the exposure of T cells to .NO had different effects on the immune response, depending on the .NO concentration and time of exposure. For instance, iNOS in T cells regulates activation-induced cell death and inhibits Treg induction. Effector CD8 T cells exposed to .NO result in the upregulation of death receptors and enhance their anti-tumor cytotoxic activity. .NO-Tregs suppress CD4 Th17 cells and their differentiation. Myeloid-derived suppressor cells (MDSCs) expressing iNOS inhibit T cell functions via .NO and inhibit anti-tumor CD8 T cells. Therefore, both .NO donors and .NO inhibitors are potential therapeutics tailored to specific target cells that regulate the T cell effector anti-tumor response.

scholarly journals CD4+T cells in ageing-associated interstitial lung abnormalities show evidence of pro-inflammatory phenotypic and functional profile

Thorax ◽  
2020 ◽  
pp. thoraxjnl-2020-215520
Author(s):  
Carlos Machahua ◽  
Ivette Buendia-Roldan ◽  
Ranferi Ocaña-Guzman ◽  
María Molina-Molina ◽  
Annie Pardo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Killer Cell ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Peripheral Blood Mononuclear ◽  
Lung Abnormalities ◽  
Immune Deficiencies

BackgroundInterstitial lung abnormalities (ILA) occur in around 10% of subjects over 60 years, and are associated with a higher rate of all-cause mortality. The pathogenic mechanisms are unclear, and the putative contribution of alterations in the immune response has not been explored. Normal ageing is associated with immune deficiencies, including Naïve T-cell decrease and greater expression of the proliferative-limiting, co-inhibitory receptor killer-cell lectin-like receptor G1 (KLRG1).ObjectiveTo evaluate the frequency and activation state of different T-cell subpopulations in ILA subjects.MethodsPeripheral blood mononuclear cells were obtained from 15 individuals with ILA, 21 age-matched controls and 28 healthy young subjects. T-cells phenotype was characterised by flow cytometry, and proliferation and activation by stimulation with anti-CD3/anti-CD28 or phorbol myristate acetate/ionomycin; KLRG1 isoforms were evaluated by western blot and cytokines were quantified by ELISA and Multiplex.ResultsA significant increase of Naïve CD4+T cells together with a decrease of central and effector memory CD4+T cells was observed in ILA compared with age-matched controls. CD4+T cells from ILA subjects exhibited greater basal proliferation, which raised after anti-CD3/anti-CD28 stimulation. Additionally, a significant increase in the levels of interleukin-6 and interferon gamma was observed in isolated CD4+T cells and plasma of ILA subjects. They also displayed fewer KLRG1+/CD4+T cells with an increase of circulating E-cadherin, the ligand of KLRG1+. No changes were observed with CD8+T cell subsets.ConclusionCD4+T cells from ILA subjects are highly proliferative and show an excessive functional activity, likely related to the loss of KLRG1 expression, which may contribute to an inflammatory state and the development of ILA.

scholarly journals Deoxynivalenol Affects Proliferation and Expression of Activation-Related Molecules in Major Porcine T-Cell Subsets

Toxins ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 644 ◽  
Author(s):  
Vatzia ◽  
Pierron ◽  
Saalmüller ◽  
Mayer ◽  
Gerner
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Animal Feed ◽  
Γδ T Cells ◽  
T Cell Subsets ◽  
Peripheral Blood Mononuclear

The Fusarium mycotoxin deoxynivalenol (DON) contaminates animal feed worldwide. In vivo, DON modifies the cellular protein synthesis, thereby also affecting the immune system. However, the functional consequences of this are still ill-defined. In this study, peripheral blood mononuclear cells from healthy pigs were incubated with different DON concentrations in the presence of Concanavalin A (ConA), a plant-derived polyclonal T-cell stimulant. T-cell subsets were investigated for proliferation and expression of CD8α, CD27, and CD28, which are involved in activation and costimulation of porcine T cells. A clear decrease in proliferation of all ConA-stimulated major T-cell subsets (CD4+, CD8+, and γδ T cells) was observed in DON concentrations higher than 0.4 µM. This applied in particular to naïve CD4+ and CD8+ T cells. From 0.8 μM onwards, DON induced a reduction of CD8α (CD4+) and CD27 expression (CD4+ and CD8+ T cells). CD28 expression was diminished in CD4+ and CD8+ T cells at a concentration of 1.6 µM DON. None of these effects were observed with the DON-derivative deepoxy-deoxynivalenol (DOM-1) at 16 µM. These results indicate that DON reduces T-cell proliferation and the expression of molecules involved in T-cell activation, providing a molecular basis for some of the described immunosuppressive effects of DON.

scholarly journals Individual Immune-Modulatory Capabilities of MSC-Derived Extracellular Vesicle (EV) Preparations and Recipient-Dependent Responsiveness

2019 ◽  
Vol 20 (7) ◽  
pp. 1642 ◽  
Author(s):  
Lambros Kordelas ◽  
Esther Schwich ◽  
Robin Dittrich ◽  
Peter Horn ◽  
Dietrich Beelen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Therapeutic Option ◽  
T Cell Response ◽  
Cytokine Profile ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Peripheral Blood Mononuclear ◽  
Vitro Assay

Treatment with extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have been suggested as novel therapeutic option in acute inflammation-associated disorders due to their immune-modulatory capacities. As we have previously observed differences in the cytokine profile of independent MSC-EV preparations, functional differences of MSC-EV preparations have to be considered. To evaluate the immune-modulatory capabilities of specific MSC-EV preparations, reliable assays are required to characterize the functionality of MSC-EV preparations prior to administration to a patient. To this end, we established an in vitro assay evaluating the immune-modulatory capacities of MSC-EV preparations. Here, we compared the efficacy of four independent MSC-EV preparations to modulate the induction of T cell differentiation and cytokine production after phorbol 12-myristate 13-acetate (PMA)/Ionomycin stimulation of peripheral blood mononuclear cells (PBMC) derived from six healthy donors. Flow cytometric analyses revealed that the four MSC-EV preparations differentially modulate the expression of surface markers, such as CD45RA, on CD4+ and CD8+ T cells, resulting in shifts in the frequencies of effector and effector memory T cells. Moreover, cytokine profile in T cell subsets was affected in a MSC-EV-specific manner exclusively in CD8+ naïve T cells. Strikingly, hierarchical clustering revealed that the T cell response towards the MSC-EV preparations largely varied among the different PBMC donors. Thus, besides defining functional activity of MSC-EV preparations, it will be crucial to test whether patients intended for treatment with MSC-EV preparations are in principal competent to respond to the envisioned MSC-EV therapy.

scholarly journals Characterization of CD4+ and CD8+ T Cell Subsets and Interferon Regulatory Factor 4 (IRF4) in MS Patients Treated with Fingolimod (FTY-720): A Follow-up Study

2018 ◽  
Author(s):  
Bahareh Laribi ◽  
Mohammad Ali Sahraian ◽  
Mehdi Shekarabi ◽  
Mohsen Marzban ◽  
Shokufeh Sadaghiani ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cd8 T Cell ◽  
T Cell Subsets ◽  
Peripheral Blood Mononuclear ◽  
Before And After ◽  
Ifn Γ ◽  
Interferon Regulatory Factor 4

Fingolimod is a novel immunomodulatory drug used in patients with relapsing multiple sclerosis (MS) which reversibly inhibits egress of lymphocytes from lymph nodes. In this longitudinal study, the frequency of Interferon- gamma (IFN-γ)+, IL4+, IL17+ and IL10+ CD4+ and CD8+ T cell subsets were measured in Fingolimod treated patients before and after 12 months’(12M) therapy using flow cytometry and compared to those of naive, Betaferon treated MS patients and healthy individuals. Additionally, the level of transcription factor IRF4 and IL-6, IL-23, TGF-β1 cytokines, required for differentiation of IL-17+ T cells, were assessed by RT-PCR and ELISA, respectively. In Fingolimod treated MS patients, we observed a significant decrease in the percentage of IFN-γ+/IL17+ CD4+ and CD8+ T cell subsets. In contrast, Fingolimod increased IL10+ CD4+ T cells. We also showed that IFN-γ+IL17+ co-producing CD8+ T cells were reduced in patients under fingolimod therapy. furthermore, Fingolimod could reduce the expression level of IRF4 in patients while IL6 was increased in the supernatant of cultured peripheral blood mononuclear cells. Our data showed that Fingolimod treatment alters CD4+ and CD8+ T cell subsets and reduces expression of IRF-4, which affects the proportion of pathogenic memory T cells in peripheral blood.

scholarly journals Potent but transient immunosuppression of T-cells is a general feature of erythroid progenitor cells

2021 ◽  
Author(s):  
Tomasz M. Grzywa ◽  
Anna Sosnowska ◽  
Zuzanna Rydzynska ◽  
Michal Lazniewski ◽  
Dariusz Plewczynski ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Progenitor Cells ◽  
Mononuclear Cells ◽  
Early Stage ◽  
Erythroid Differentiation ◽  
Peripheral Blood Mononuclear ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells

AbstractErythroid progenitor cells (EPCs) have been recently recognized as potent immunoregulatory cells with defined roles in fetomaternal tolerance and immune response to infectious agents in neonates and cancer patients. Here, we show that early-stage EPCs are enriched in anemia, have high levels of arginase 2 (ARG2) and reactive oxygen species (ROS). EPCs expansion in anemic mice leads to the L-arginine depletion in the spleen microenvironment resulting in the suppression of T-cell responses. In humans with anemia, EPCs expand and express both ARG1 and ARG2 that participate in suppressing the proliferation and production of IFN-γ from T-cells. EPCs differentiated from peripheral blood mononuclear cells potently suppress T-cell proliferation and this effect is the most prominent for CD49dhi CD71hiEPCs. The suppressive properties disappear during erythroid differentiation as more differentiated EPCs as well as mature erythrocytes lack significant immunoregulatory properties. Our studies provide a novel insight into the role of EPCs in the regulation of immune response.Abstract Figure

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