Immunization with Salmonella Enteritidis secreting mucosal adjuvant labile toxin confers protection against wild type challenge via augmentation of CD3 + CD4 + T-cell proliferation and enhancement of IFN-γ, IL-6 and IL-10 expressions in chicken

Vaccine ◽  
2017 ◽  
Vol 35 (5) ◽  
pp. 767-773 ◽  
Author(s):  
Jonathan Lalsiamthara ◽  
John Hwa Lee
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Salmonella Enteritidis ◽  
Cd4 T Cell ◽  
T Cell Proliferation ◽  
Wild Type ◽  
Mucosal Adjuvant ◽  
Ifn Γ

scholarly journals Multiple Myeloma Cell-Derived Interleukin-32gamma Increases the Immunosuppressive Function of Macrophages By Promoting Indoleamine 2,3-Dioxygenase (IDO) Expression

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3179-3179
Author(s):  
Haimeng Yan ◽  
Donghua He ◽  
Xi Huang ◽  
Zhang En Fan ◽  
He Huang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
T Cell ◽  
Rna Sequencing ◽  
Cd4 T Cell ◽  
T Cell Proliferation ◽  
Indoleamine 2,3 Dioxygenase ◽  
Tnf Α ◽  
Ifn Γ

Abstract Background: The interaction of multiple myeloma (MM) cells with macrophages (MΦs) in the bone marrow microenvironment contributes to the pathophysiology of MM. In addition to promoting angiogenesis through vasculogenic mimicry, MM-associated MΦs (mMΦs) protect MM cells from spontaneous and chemotherapy-induced apoptosis. mMΦs therefore represent a potential target for myeloma treatment and it is essential to explore the mechanisms underlying normal MΦ polarization to mMΦs. We previously showed that IL-32 is overexpressed in MM patients and is mainly derived from MM cells. The present study was designed to explore the clinical significance of IL-32 in MM and to further elucidate the molecular mechanisms underlying the IL-32-mediated immune function of MΦs. Methods: We examined the expression of IL-32 in bone marrow biopsy samples using immunohistochemistry. Quantitative real-time PCR, western blot analysis and immunofluorescence were applied to measure the expression of IL-32, IDO and proteinase 3 (PR3). We obtained the global transcriptional profile of the IL-32γ-treated MΦs by RNA sequencing (RNA-Seq). Immunoprecipitation (IP) and GST pulldown experiments was applied to confirm the binding affinity of PR3 for IL-32. We created IL-32-knockdown MM cells by transfection of IL-32 shRNA and silenced PR3 expression in MΦs using siRNA targeting PR3. CD4+ T cell proliferation and IL-2, IFN-γ and TNF-α production were measured by flow cytometry. Results: We found that high IL-32 expression in MM patients was associated with advanced clinical stage and high serum β2-microglobulin levels. Several isoforms of IL-32 were detected in MM cells and IL-32γ was the most active subtype. RNA sequencing revealed that IL-32γ significantly induced the production of the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO) in MΦs and this effect was verified at the protein level. Furthermore, IL-32-knockdown MM cells showed less ability than control MM cells to promote IDO expression. As a binding protein for IL-32, PR3 was universally expressed on the surface of MΦs and knockdown of PR3 or inhibition of the STAT3 and nuclear factor κB (NF-κB) pathways hindered the IL-32γ-mediated stimulation of IDO expression. Finally, IDO-positive IL-32γ-educated MΦs inhibited CD4+ T cell proliferation and IL-2, IFN-γ and TNF-α production in response to activation. Conclusion: Our study showed that MM cell-derived IL-32γ induced IDO production in MΦs through PR3 and the downstream STAT3 and NF-κB pathways, resulting in the suppression of the proliferation and effector function of CD4+ T cells. High IL-32 expression in MM may contribute to an immunosuppressive microenvironment by upregulating IDO production in MΦs and promote MM progression. Disclosures No relevant conflicts of interest to declare.

The role of SAP in murine CD150 (SLAM)-mediated T-cell proliferation and interferon γ production

Blood ◽  
2002 ◽  
Vol 100 (8) ◽  
pp. 2899-2907 ◽  
Author(s):  
Duncan Howie ◽  
Susumo Okamoto ◽  
Svend Rietdijk ◽  
Kareem Clarke ◽  
Ninghai Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cell Surface ◽  
Dna Synthesis ◽  
Interferon Γ ◽  
T Cell Proliferation ◽  
Wild Type ◽  
Ifn Γ

CD150 (signaling lymphocyte activation molecule [SLAM]) is a self-ligand cell surface glycoprotein expressed on T cells, B cells, macrophages, and dendritic cells. To further explore the role of CD150 signaling in costimulation and TH1 priming we have generated a panel of rat antimouse CD150 monoclonal antibodies. CD150 cell surface expression is up-regulated with rapid kinetics in activated T cells and lipopolysaccharide/interferon γ (IFN-γ)–activated macrophages. Anti-CD150 triggering induces strong costimulation of T cells triggered through CD3. DNA synthesis of murine T cells induced by anti-CD150 is not dependent on SLAM-associated protein (SAP, SH2D1A), because anti-CD150 induces similar levels of DNA synthesis in SAP−/− T cells. Antibodies to CD150 also enhance IFN-γ production both in wild-type and SAP−/− T cells during primary stimulation. The level of IFN-γ production is higher in SAP−/− T cells than in wild-type T cells. Anti-CD150 antibodies also synergize with interleukin 12 (IL-12) treatment in up-regulation of IL-12 receptor β2 mRNA during TH1 priming, and inhibit primary TH2 polarization in an IFN-γ–dependent fashion. Cross-linking CD150 on CD4 T cells induces rapid serine phosphorylation of Akt/PKB. We speculate that this is an important pathway contributing to CD150-mediated T-cell proliferation.

scholarly journals Blockade of B7-H1 on Macrophages Suppresses CD4+ T Cell Proliferation by Augmenting IFN-γ-Induced Nitric Oxide Production

2005 ◽  
Vol 175 (3) ◽  
pp. 1586-1592 ◽  
Author(s):  
Tomohide Yamazaki ◽  
Hisaya Akiba ◽  
Akemi Koyanagi ◽  
Miyuki Azuma ◽  
Hideo Yagita ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Proliferation ◽  
T Cell ◽  
Cd4 T Cell ◽  
T Cell Proliferation ◽  
Nitric Oxide Production ◽  
Oxide Production ◽  
Ifn Γ

scholarly journals Naturally Occurring Altered Peptide Ligands ControlSalmonella-Specific CD4+T Cell Proliferation, IFN-γ Production, and Protective Potency

2009 ◽  
Vol 184 (2) ◽  
pp. 869-876 ◽  
Author(s):  
Tanner M. Johanns ◽  
James M. Ertelt ◽  
Joseph C. Lai ◽  
Jared H. Rowe ◽  
Ross A. Avant ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Peptide Ligands ◽  
Cd4 T Cell ◽  
T Cell Proliferation ◽  
Altered Peptide Ligands ◽  
Naturally Occurring ◽  
Ifn Γ

Stat3 Activation in Donor CD4 T-Cells Is Critical for Acute Gvhd

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1906-1906
Author(s):  
Katsutoshi Ozaki ◽  
Haruko Matsu ◽  
Keiko Hatanaka ◽  
Akiko Meguro ◽  
Iekuni Oh ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Acute Gvhd ◽  
Conflicts Of Interest ◽  
Cd4 T Cell ◽  
T Cell Proliferation ◽  
Intrinsic Defect ◽  
Wild Type

Abstract Abstract 1906 Stat3-deficient (Stat3KO) T-cells reportedly are less proliferative due to accelerated apoptosis in the presence of IL-6, and have suppressed IL-2Ra expression. There are conflicting mouse model results concerning Stat3 in graft-versus-host disease (GVHD). Previously, we demonstrated IL-21 signaling is essential for GVHD. As Stat3 is a downstream signaling molecule, clarifying its role in GVHD T-cells is important. After co-transplantation of bone marrow and wild-type or Stat3KO CD4+ T-cells, recipients of the latter developed attenuated GVHD with longer survival than recipients of the former, and their splenic CD4+ T-cells exhibited a profound proliferation defect in the mixed lymphocyte reaction (MLR). In contrast to IL-21R-deficient CD4+ T-cells, pre-transplantation Stat3KO CD4+ T-cells showed similar MLR impairment, suggesting an intrinsic defect. Consistently, proliferation in low-dose anti-CD3 stimulation was defective, but MLR apoptosis was not increased. Neutralizing antibody against IL-2, but not IL-6R, suppressed MLR wild-type CD4 T-cell proliferation, suggesting Stat3KO CD4+ T-cells' MLR apoptosis might be attributed to lack of IL-6 contribution. Pallandre et al. reported Stat3 ablation in CD4 exacerbated GVHD, speculating Stat3 depletion suppressed regulatory T-cell function, leading to accelerated GVHD. Lu et al. analyzed T-cell phosphorylated proteins during allo-activation, demonstrating Stat3 and Erk1/2 are important for this and GVHD. Radojcic et al. showed Stat3KO T-cells cannot induce chronic cutaneous GVHD because of repressed CD4 proliferation and loss of Th17 differentiation. Reasons for differing conclusions are unknown. One possibility is enhanced innate immunity induced by Stat3-siRNA-transduced stem and progenitor cells, consistent with several reports. Our use of Stat3KO T-cells overcame this problem. The latter two reports are consistent with our results. To our knowledge, we report the first direct evidence Stat3 activation in donor CD4+ T-cells is critical for acute GVHD. Durant et al. delineated detailed gene regulation in Stat3KO CD4+ T-cells, and one of their conclusions—Stat3 is important for CD4+ T-cell proliferation—is consistent with our results. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impaired Induction of CD27 and CD28 Predicts Naive CD4 T Cell Proliferation Defects in HIV Disease

2007 ◽  
Vol 179 (6) ◽  
pp. 3543-3549 ◽  
Author(s):  
Angel A. Luciano ◽  
Michael M. Lederman ◽  
Alice Valentin-Torres ◽  
Douglas A. Bazdar ◽  
Scott F. Sieg
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Cd4 T Cell ◽  
T Cell Proliferation ◽  
Hiv Disease
Sign in / Sign up

Export Citation Format

Share Document