scholarly journals Polyphenols and phenolic acids modulate inflammatory cytokine release by Jurkat human CD4+ T‐cells

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Christopher Thomas Ford ◽  
Sian Richardson ◽  
Francis McArdle ◽  
Alan Crozier ◽  
Anne McArdle ◽  
...  
Keyword(s):  
T Cells ◽  
Phenolic Acids ◽  
Cd4 T Cells ◽  
Inflammatory Cytokine ◽  
Cytokine Release

scholarly journals HIV-Infected Children Have Elevated Levels of PD-1+ Memory CD4 T Cells With Low Proliferative Capacity and High Inflammatory Cytokine Effector Functions

2017 ◽  
Vol 216 (6) ◽  
pp. 641-650 ◽  
Author(s):  
Julia Foldi ◽  
Lina Kozhaya ◽  
Bret McCarty ◽  
Mussa Mwamzuka ◽  
Fatma Marshed ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Inflammatory Cytokine ◽  
Proliferative Capacity ◽  
Effector Functions ◽  
Memory Cd4 T Cells

Abstract 033: Differential Vasopressin Receptor Expression on CD4+ T Cells from Mouse and Human Preeclamptic Pregnancies

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Sabrina M Scroggins ◽  
Donna A Santillan ◽  
Jenna M Peterson ◽  
Nicole A Pearson ◽  
Jeremy A Sandgren ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Immune Modulation ◽  
Inflammatory Cytokine ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Cell Activity ◽  
Tissue Bank ◽  
Receptor Expression ◽  
Inflammatory Cytokine Production

The pathogenesis of preeclampsia (PreE) involves the failure of the maternal immune system to normally tolerate the pregnancy. Inflammatory cytokines are elevated in PreE-affected women with a concurrent decrease in anti-inflammatory cytokine production. Consistent with what other groups have observed in mouse models of hypertension during pregnancy and in human PreE-affected pregnancies, we observed increased inflammatory cytokine production and CD4+ T helper populations in our chronic infusion of vasopressin (AVP) mouse model of PreE. The mechanisms of immune modulation by AVP have not been elucidated. As increased T cell activity is involved in the development of PreE, the objective of this study was to investigate if CD4+ T cells express AVP receptors. Splenic CD4+ T cells were negatively purified from C57BL/6J saline and AVP-infused (24 ng/hour) dams. Expression of AVP receptors (AVPR) 1a, 1b, 2, and the aminopeptidase LNPEP (catalyzes AVP degradation) was determined via qPCR. Raw cycle threshold (Ct) values were normalized (ΔCt) against the 18S rRNA endogenous control. Mouse CD4+ T cells express all AVP receptors and LNPEP. By ANOVA, AVPR2 is the highest expressed receptor in CD4+ T cells from saline (N=7, p=0.002) and AVP-infused (N=10, p<0.0001) dams. Human maternal mononuclear cells, obtained from the University of Iowa Maternal-Fetal Tissue Bank (IRB #200910784) from control and PreE-affected women, were similarly analyzed. As in mouse CD4+ T cells, human control (N=27, p<0.0001) and PreE-affected (N=26, p<0.0001) CD4+ T cells most highly expressed AVPR2. AVPR1a was also highly expressed while AVPR1b was the least expressed. CD4+ T cells isolated from human PreE-affected women expressed significantly lower AVPR1a (10.0±0.3 N=27 vs. 11.1±0.2 N=0.23, p=0.009) and increased LNPEP (17.2±0.5 N=27 vs. 15.1±0.3 N=26, p=0.001) than controls. Here, we demonstrate CD4+ T cells, both mouse and human, express AVP receptors and that 1a and 2 are highest expressed. Although the actions of AVP on the vasculature are primarily mediated through AVPR1a, these data suggest AVP may differentially act through AVPR1a to mediate immune responses during PreE.

scholarly journals Elevated vasopressin in pregnant mice induces T-helper subset alterations consistent with human preeclampsia

2018 ◽  
Vol 132 (3) ◽  
pp. 419-436 ◽  
Author(s):  
Sabrina M. Scroggins ◽  
Donna A. Santillan ◽  
Jenna M. Lund ◽  
Jeremy A. Sandgren ◽  
Lindsay K. Krotz ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Inflammatory Cytokine ◽  
Maternal Plasma ◽  
Hypertensive Disorder ◽  
Wild Type ◽  
T Helper ◽  
Anti Inflammatory ◽  
Immune Changes ◽  
Anti Inflammatory Cytokine

The pathogenesis of preeclampsia (PreE), a hypertensive disorder of pregnancy, involves imbalanced T helper (TH) cell populations and resultant changes in pro- and anti-inflammatory cytokine release. Elevated copeptin (an inert biomarker of arginine vasopressin (AVP)), secretion precedes the development of symptoms in PreE in humans, and infusion of AVP proximal to and throughout gestation is sufficient to initiate cardiovascular and renal phenotypes of PreE in wild-type C57BL/6J mice. We hypothesize that AVP infusion in wild-type mice is sufficient to induce the immune changes observed in human PreE. AVP infusion throughout gestation in mice resulted in increased pro-inflammatory interferon γ (IFNg) (TH1) in the maternal plasma. The TH17-associated cytokine interleukin (IL)-17 was elevated in the maternal plasma, amniotic fluid, and placenta following AVP infusion. Conversely, the TH2-associated anti-inflammatory cytokine IL-4 was decreased in the maternal and fetal kidneys from AVP-infused dams, while IL-10 was decreased in the maternal kidney and all fetal tissues. Collectively, these results demonstrate the sufficiency of AVP to induce the immune changes typical of PreE. We investigated if T cells can respond directly to AVP by evaluating the expression of AVP receptors (AVPRs) on mouse and human CD4+ T cells. Mouse and human T cells expressed AVPR1a, AVPR1b, and AVPR2. The expression of AVPR1a was decreased in CD4+ T cells obtained from PreE-affected women. In total, our data are consistent with a potential initiating role for AVP in the immune dysfunction typical of PreE and identifies putative signaling mechanism(s) for future investigation.

Changes in cytokine release by CD4+ T cells in HIV1 infection

1994 ◽  
Vol 145 (8-9) ◽  
pp. 607-611 ◽  
Author(s):  
L. Meyaard ◽  
F. Miedema
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Release ◽  
Hiv1 Infection

Decreased MIR-425 Induced Inflammatory Cytokine Production via N-RAS Upregulation in CD4+ T Cells of Primary Biliar Cholangitis

2016 ◽  
Vol 64 (2) ◽  
pp. S643-S644
Author(s):  
R. Nakagawa ◽  
R. Muroyama ◽  
K. Koike ◽  
C. Saeki ◽  
S. Ito ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Inflammatory Cytokine Production

scholarly journals A Sensitive Whole Blood Assay Detects Antigen-Stimulated Cytokine Release From CD4+ T Cells and Facilitates Immunomonitoring in a Phase 2 Clinical Trial of Nexvax2 in Coeliac Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Melinda Y. Hardy ◽  
Gautam Goel ◽  
Amy K. Russell ◽  
Swee Lin G. Chen Yi Mei ◽  
Gregor J. E. Brown ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cells ◽  
Whole Blood ◽  
Cd4 T Cells ◽  
Phase 2 ◽  
Cytokine Release ◽  
Gluten Peptides ◽  
Gluten Peptide ◽  
Phase 2 Clinical Trial ◽  
Ifn Γ

Improved blood tests assessing the functional status of rare gluten-specific CD4+ T cells are needed to effectively monitor experimental therapies for coeliac disease (CD). Our aim was to develop a simple, but highly sensitive cytokine release assay (CRA) for gluten-specific CD4+ T cells that did not require patients to undergo a prior gluten challenge, and would be practical in large, multi-centre clinical trials. We developed an enhanced CRA and used it in a phase 2 clinical trial (“RESET CeD”) of Nexvax2, a peptide-based immunotherapy for CD. Two participants with treated CD were assessed in a pilot study prior to and six days after a 3-day gluten challenge. Dye-dilution proliferation in peripheral blood mononuclear cells (PBMC) was assessed, and IL-2, IFN-γ and IL-10 were measured by multiplex electrochemiluminescence immunoassay (ECL) after 24-hour gluten-peptide stimulation of whole blood or matched PBMC. Subsequently, gluten-specific CD4+ T cells in blood were assessed in a subgroup of the RESET CeD Study participants who received Nexvax2 (maintenance dose 900 μg, n = 12) or placebo (n = 9). The pilot study showed that gluten peptides induced IL-2, IFN-γ and IL-10 release from PBMCs attributable to CD4+ T cells, but the PBMC CRA was substantially less sensitive than whole blood CRA. Only modest gluten peptide-stimulated IL-2 release could be detected without prior gluten challenge using PBMC. In contrast, whole blood CRA enabled detection of IL-2 and IFN-γ before and after gluten challenge. IL-2 and IFN-γ release in whole blood required more than 6 hours incubation. Delay in whole blood incubation of more than three hours from collection substantially reduced antigen-stimulated IL-2 and IFN-γ secretion. Nexvax2, but not placebo treatment in the RESET CeD Study was associated with significant reductions in gluten peptide-stimulated whole blood IL-2 and IFN-γ release, and CD4+ T cell proliferation. We conclude that using fresh whole blood instead of PBMC substantially enhances cytokine secretion stimulated by gluten peptides, and enables assessment of rare gluten-specific CD4+ T cells without requiring CD patients to undertake a gluten challenge. Whole blood assessment coupled with ultra-sensitive cytokine detection shows promise in the monitoring of rare antigen-specific T cells in clinical studies.

Abrogation of Donor T Cell IL-21 Signaling Leads to Tissue-Specific Modulation of Immunity and Separation of Gvhd From GVL

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 729-729
Author(s):  
Alan M. Hanash ◽  
Lucy W. Kappel ◽  
Nury L. Yim ◽  
Rebecca A. Nejat ◽  
Gabrielle L. Goldberg ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Inflammatory Cytokine ◽  
Wild Type ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Donor T Cells

Abstract Abstract 729 Allogeneic hematopoietic transplantation is frequently the only curative therapy available to patients with hematopoietic malignancies, however transplant success continues to be limited by complications including graft vs. host disease (GVHD) and disease relapse. Separation of GVHD from graft vs. leukemia/lymphoma (GVL) responses continues to be a major goal of experimental and clinical transplantation, and better understanding of T cell immunobiology may lead to novel strategies to accomplish this goal. Interleukin 21 (IL-21) is a pro-inflammatory cytokine produced by Th17 helper T cells, and abrogation of IL-21 signaling has recently been demonstrated to reduce GVHD while retaining GVL. However, the mechanisms by which IL-21 may lead to a separation of GVHD and GVL are incompletely understood. In order to characterize the effect of IL-21 on GVH and GVL T cell responses, we compared wild type and IL-21 receptor knockout (IL-21R KO) donor T cells in a C57BL/6 into BALB/c murine MHC-mismatched bone marrow transplant (BMT) model. Lethally irradiated BMT recipients of IL-21R KO T cells demonstrated decreased GVHD-related morbidity (p<.05) and mortality (p<.01), and decreased histopathologic evidence of GVHD within the small intestine (p<.05). While this reduction in IL-21R KO T cell-mediated GVHD was associated with increased donor regulatory T cells two to three weeks post-BMT (p<.001), IL-21 signaling in both donor CD4 and donor CD8 T cells was found to contribute to GVHD mortality (p<.01 for CD4, p<.05 for CD8). Analysis of IL-21R expression by wild type T cells demonstrated receptor upregulation upon polyclonal activation in vitro and upon alloactivation in vivo (p<.01). However, this IL-21R upregulation was not required for in vivo alloactivation, as IL-21R KO and wild type donor T cells demonstrated equivalently greater proliferation in allogeneic vs. syngeneic recipients (p<.001), equivalent upregulation of CD25 (p<.001), and equivalent downregulation of CD62L (p<.01 for CD8 T cells). Despite this equivalent alloactivation, IL-21R KO T cells demonstrated decreased infiltration within the small intestine (p<.05), decreased infiltration in mesenteric lymph nodes (p<.05 for CD8 T cells, p<.001 for CD4 T cells), and decreased inflammatory cytokine-producing CD4 T cells within mesenteric lymph nodes (p<.01 for IFN-g, p<.001 for TNF-a, Figure 1A). Consistent with this, transplanted IL-21R KO donor T cells demonstrated decreased expression of a4b7 integrin (LPAM, p<.05), a molecule known to be involved in homing of GVHD-mediating donor T cells to the gut. However, in contrast to the reduced inflammatory cytokine-producing CD4 T cells observed in mesenteric lymph nodes, IL-21R KO helper T cell cytokine production was maintained in spleen (Figure 1B) and peripheral lymph nodes, and IL-21R KO T cells were able to protect recipient mice from lethality due to A20 lymphoma (p<.001). In summary, abrogation of IL-21 signaling in donor T cells leads to tissue-specific modulation of immunity, such that gastrointestinal GVHD is reduced, but peripheral T cell function and GVL capacity are retained. Targeting IL-21 for therapeutic intervention is an exciting strategy to separate GVHD from GVL, and this novel approach should be considered for clinical investigation to improve transplant outcomes and prevent malignant relapse. Disclosures: No relevant conflicts of interest to declare.

Inhibition of pro-inflammatory cytokine generation by CTLA4-Ig in the skin and colon of mice adoptively transplanted with CD45RBhi CD4+ T cells correlates with suppression of psoriasis and colitis

2002 ◽  
Vol 2 (5) ◽  
pp. 653-672 ◽  
Author(s):  
Colleen M Davenport ◽  
Holly Ann McAdams ◽  
Jen Kou ◽  
Kirsten Mascioli ◽  
Christopher Eichman ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Inflammatory Cytokine

scholarly journals Potential role of MRN-100, an iron-based compound, in upregulating production of cytokine IL-10 in human dendritic cells to promote an anti-inflammatory response in vitro

2019 ◽  
Vol 33 ◽  
pp. 205873841984493
Author(s):  
Mamdooh H Ghoneum ◽  
James K Gimzewski ◽  
Aya D Ghoneum ◽  
Sudhanshu Agrawal
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Inflammatory Cytokine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Functional Assay ◽  
Iron Based ◽  
Anti Inflammatory ◽  
Human Dendritic Cells

The hydroferrate fluid MRN-100, an iron-based compound with potent antioxidant characteristics, was examined to identify its possible anti-inflammatory effects on human dendritic cells (DCs) in vitro. Human monocyte–derived DCs were treated with MRN-100 at two concentrations (50 and 100 μL/mL) for 24 h and then stimulated with or without lipopolysaccharides (LPS). The expression of DC maturation markers was assessed by flow cytometry and the production of cytokines was determined by enzyme-linked immunosorbent assay (ELISA). Functional assay was performed by co-culturing MRN-100-treated and untreated DCs with allogeneic naïve CD4+ T cells and assaying the T cells’ cytokine production. Results show that treatment with MRN-100 significantly upregulated the co-stimulatory molecules CD80 and CD86 and increased human leukocyte antigen-DR (HLA-DR) though not significantly. MRN-100 treatment also significantly increased the production of the anti-inflammatory cytokine interleukin (IL)-10. On the other hand, MRN-100 significantly induced the secretion of pro-inflammatory cytokines such as IL-6 only at high concentrations. Furthermore, DCs pretreated with MRN-100 and either stimulated or not with LPS were able to prime CD4+ T cells to secrete significant amounts of IL-10 while inhibiting the secretion of pro-inflammatory cytokine tumor necrosis factor (TNF)-α. These results indicate that MRN-100 is a powerful anti-inflammatory agent that promotes the generation of an anti-inflammatory immune response in vitro. MRN-100 could be beneficial for treating patients with inflammatory diseases, including arthritis and type 1 diabetes, and its potential benefits should be examined in clinical trials.

JQ 1, a Selective Bromodomain Inhibitor, Decreased the Expression of the Tolerogenic Molecule PDL1 in Antigen-Presenting Cells (APCs) and Restores the Responsiveness of Anergic CD4+ T Cells

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2749-2749 ◽  
Author(s):  
Hongwei Wang ◽  
Fengdong Cheng ◽  
Limin Xing ◽  
Xiaohong Zhao ◽  
Alejandro Villagra ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Inflammatory Cytokine ◽  
Conflicts Of Interest ◽  
Specific Inhibitor ◽  
Inflammatory Status ◽  
Bet Inhibitors ◽  
Cognate Antigen ◽  
Antigen Presenting

Abstract Bromodomain and extraterminal (BET) is a protein domain that recognizes acetylated lysine residues such as those on the N-terminal tails of histones. This recognition is often a prerequisite for protein-histone association, chromatin remodeling and gene transcription. The role of BET proteins in regulating the response of inflammatory cytokine genes through translation of histone marks is poorly understood. Given that the inflammatory status of the APC is critical in determining T-cell activation versus T-cell tolerance and that epigenetic modifications of specific genes in the APC play a key role in this process, we recently determined the functional consequences of inhibiting BET in APCs. First, we evaluated the effects of JQ 1, a selective small-molecule BET bromodomain inhibitor on APC’s function and its regulation of antigen-specific CD4+ T-cells response. In vitro treatment of peritoneal elicited macrophages (PEM) or bone marrow derived dendritic cells (DCs) with increasing concentrations of JQ 1 resulted in decreased expression and protein production of the anti-inflammatory cytokine IL-10 and IL-6 in response to LPS stimulation. At the concentration used, JQ 1 did not affect the viability of treated APCs. Second, analysis of the expression of MHC class molecules and co-stimulatory molecules revealed a decreased expression of the tolerogenic PDL1 molecule in JQ 1- treated APCs as compared to untreated APCs. Third, we evaluated the ability of JQ 1 treated APCs to present cognate antigen to naïve or tolerant antigen-specific CD4+ T-cells. We found that treatment of either PEM or DC with JQ 1 enhanced their antigen-presenting capabilities leading to effective priming of naïve CD4+ T-cells confirmed by their increased production of IL-2 and IFN-gamma in response to cognate antigen. More importantly, JQ 1- treated APCs were able to restore the responsiveness of tolerant CD4+ T-cells isolated from lymphoma bearing hosts. Taken together, we have found that APCs treated with the Bromodomain specific inhibitor JQ 1 are more inflammatory, display lower expression of the immunosuppressive molecule PDL1 and more importantly, are capable of restoring the responsiveness of tolerant T-cells. Our studies therefore have unveiled a previously unknown immunological effect of BET inhibitors and have broadened their clinical scope as promising adjuvants in cancer immunotherapy. Disclosures No relevant conflicts of interest to declare.

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