Immunomodulating Effects of Fractioned Polysaccharides Isolated from Yu-Ping-Feng-Powder in Cyclophosphamide-Treated Mice

2006 ◽  
Vol 34 (04) ◽  
pp. 631-641 ◽  
Author(s):  
Xiang-Tao Chen ◽  
Jun Li ◽  
Hui-Li Wang ◽  
Wen-Ming Cheng ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
High Probability ◽  
Delayed Type Hypersensitivity ◽  
T Cell Proliferation ◽  
Splenocyte Proliferation ◽  
Active Components ◽  
Humoral And Cellular Immunity ◽  
Medicine Prescription ◽  
Chinese Medicine Prescription ◽  
Ifn Γ

Yu-Ping-Feng-Powder (YP), a traditional Chinese medicine prescription, is widely applied in China for the cure and prevention of diseases related to immunodeficiency. To test whether the fractioned polysaccharides (YPF-P) isolated from YP have immunomodulating activities, the effects of YPF-P on cyclophosphamide (Cy)-treated mice were studied in relation to phagocytosis of macrophage, splenocyte proliferation, and humoral, and cellular immunity parameters. It was found that YPF-P enhances phagocytic activity, augments ConA- or LPS-stimulated T cell proliferation, increases the quantitative haemolysis of SRBC (QHS) and delayed-type hypersensitivity reaction (DTH) to dinitrofluorobenzene. Hence, YPF-P restored the immuno-competence suppressed by Cy. YPF-P also augmented IL-2 and IFN-γ production, but failed to increase IL-4 production, which indicates that there is high probability that it enhance Th1 function. These results suggested that YPF-P has immunomodulating effects and that the polysaccharides constitute one of the active components of YP.

scholarly journals The Role of Interleukin-10 (IL-10) in IL-15–Mediated T-Cell Responses

Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4513-4521 ◽  
Author(s):  
Dieter Körholz ◽  
Ursula Banning ◽  
Halvard Bönig ◽  
Markus Grewe ◽  
Marion Schneider ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Interleukin 10 ◽  
T Cell Proliferation ◽  
Cell Production ◽  
Cd25 Expression ◽  
Tnf Α ◽  
Ifn Γ

Abstract Interleukin-15 (IL-15) is a potent T-cell stimulating factor, which has recently been used for pre-clinical in vivo immunotherapy. Here, the IL-15 effect on CD3-stimulated peripheral human T cells was investigated. IL-15 induced a significant T-cell proliferation and upregulated CD25 expression. IL-15 significantly enhanced T-cell production of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and IL-10. Between 10- and 100-fold greater concentrations of IL-15 were necessary to reach a biological effect equivalent to that of IL-2. Blockade of IL-2 binding to the high-affinity IL-2 receptor did not affect the IL-15 effects, suggesting that IL-15 did not act by inducing endogenous IL-2. Exogenously administered IL-10 significantly reduced the IL-15 and IL-2–mediated IFN-γ and TNF-α production, whereas T-cell proliferation and CD25 expression were not affected. The inhibitory effects of exogenously administered IL-10 on T-cell cytokine production appeared indirect, and are likely secondary to decreased IL-12 production by accessory cells. Inhibition of endogenous IL-10 binding to the IL-10 receptor significantly increased IFN-γ and TNF-α release from T cells. These data suggest that endogenous IL-10 can regulate activated T-cell production of IFN-γ and TNF-α via a paracrine negative feedback loop. The observations of this study could be of relevance for the therapeutic use of IL-15 in vivo.

Nitric oxide-producing CD11b+Ly-6G(Gr-1)+CD31(ER-MP12)+cells in the spleen of cyclophosphamide–treated mice: implications for T-cell responses in immunosuppressed mice

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 212-220 ◽  
Author(s):  
Iñigo Angulo ◽  
Federico Gómez de las Heras ◽  
José F. Garcı́a-Bustos ◽  
Domingo Gargallo ◽  
M. Angeles Muñoz-Fernández ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Proliferation ◽  
T Cell ◽  
T Cell Responses ◽  
T Cell Proliferation ◽  
Intensive Chemotherapy ◽  
Suppressive Activity ◽  
Cell Responses ◽  
Nos Inhibitors ◽  
Ifn Γ

Abstract During recovery from intensive chemotherapy with cyclophosphamide (CTX), mice suffer a severe but transitory impairment in spleen cell proliferation to T-cell mitogens (Con A or anti-CD3 plus IL-2). Although CTX treatment reduced spleen T-cell cellularity, this cannot fully account for T-cell unresponsiveness. The results showed that CTX induces the colonization of spleen by an immature myeloid CD11b+Ly-6G+CD31+ population. Its presence closely correlated with the maximum inhibition of T-cell proliferation. Moreover, this suppressive activity was dependent on nitric oxide (NO) production in cultures since (1) higher amounts of nitric oxide and inducible nitric oxide synthase (iNOS) mRNA were produced in CTX spleen cells (CTX-SC) than in control splenocyte cultures and (2) NOS inhibitors greatly improved the proliferation of T lymphocytes. Nitric oxide production and suppressive activity were also dependent on endogenous interferon-γ (IFN-γ) production since anti–IFN-γ abrogated both effects. Finally, iNOS protein expression was restricted to a heterogeneous population of CD31+cells in which CD11b+Ly-6G+ cells were required to suppress T-cell proliferation. These results indicated that CTX might also cause immunosuppression by a mechanism involving the presence of immature myeloid cells with suppressor activity. This may have implications in clinical praxis since inappropriate immunotherapies in patients treated with intensive chemotherapy could lead to deleterious T-cell responses. (Blood. 2000;95:212-220)

scholarly journals Enhanced IFN-γ, but not IL-2, response to Mycobacterium tuberculosis antigens in HIV/latent TB co-infected patients on long-term HAART

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Girmay Desalegn ◽  
Aster Tsegaye ◽  
Dawit Gebreegziabiher ◽  
Abraham Aseffa ◽  
Rawleigh Howe
Keyword(s):  
Cell Proliferation ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Proliferation ◽  
Median Frequency ◽  
Immune Restoration ◽  
Latent Tb ◽  
Ifn Γ

Abstract Background HIV-infected individuals with latent TB infection are at increased risk of developing active TB. HAART greatly reduces the incidence rate of TB in HIV-infected patients and reconstitutes Mycobacterium tuberculosis (M. tuberculosis)-specific immune response in the first 12 months of therapy. The durability of the anti-mycobacterial immune restoration after a year of HAART however remains less investigated. Method A cross-sectional study was conducted to evaluate M. tuberculosis-specific functional immune responses in HIV/latent TB co-infected patients who were on HAART for at least 1.5 up to 9 years as compared to HAART-naïve patients. Three-hundred sixteen HIV-infected patients without active TB were screened by tuberculin skin testing for M. tuberculosis infection and peripheral blood mononuclear cells (PBMCs) were isolated from 61 HIV/latent TB co-infected patients (30 HAART-naïve and 31 HAART-treated). IFN-γ and IL-2 ELISPOT as well as CFSE cell proliferation assays were performed after stimulation with M. tuberculosis antigens PPD and ESAT-6. Result The median frequency of PPD and ESAT-6 specific IFN-γ secreting cells was significantly higher in the HAART-treated patients as compared to HAART-naïve patients, p = 0.0021 and p = 0.0081 respectively. However, there was no significant difference in the median frequency of IL-2 secreting cells responding to PPD (p = 0.5981) and ESAT-6 (p = 0.3943) antigens between HAART-naïve and-treated groups. Both IFN-γ and IL-2 responses were independent of CD4+ T cell count regardless of the HAART status. Notably, the frequency of PPD and ESAT-6 specific IL-2 secreting cells was positively associated with CD4+ T cell proliferation while inversely correlated with duration of HAART, raising the possibility that M. tuberculosis-specific IL-2 response that promote the antigen-specific CD4+ T cell proliferation diminish with time on antiretroviral therapy in HIV/latent TB co-infected patients. Conclusion This study shows an increased M. tuberculosis-specific IFN-γ, but not IL-2, response in HIV/latent TB co-infected patients with long-term HAART, consistent with only partial immune restoration. Future studies should, therefore, be done to prospectively define the rate and extent to which functional immune responses to M. tuberculosis are restored after long-term HAART.

CD11b+gr-1+ myeloid Derived Suppressor Cells (MDSC) In Normal Bone Marrow Suppress T Cell Proliferation and Enhance T-Regulatory Function Via a IL10-, IL4- and IDO-Independent Mechanism

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4801-4801 ◽  
Author(s):  
Parvin Forghani ◽  
Wayne Harris ◽  
jian-Ming Li ◽  
M.R. Khorramizadeh ◽  
Edmund Waller
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Regulatory Function ◽  
T Cell Proliferation ◽  
Suppressive Activity ◽  
Ifn Γ

Abstract Abstract 4801 MDSC have been described as an important negative regulators of autologous anti-cancer immune responses. Considering the important role of MDSC in immune regulation in allogenic stem cell and organ transplantation, we undertook an investigation of the mechanism(s) by which MDSC inhibit T–cell activation and proliferation, and tested the hypothesis that local cytokine secretion or IDO activity is required for suppression of T-cell proliferation. Two separate populations CD11bhiGr-1hi and CD11bhi Gr-1int were isolated by high-speed FACS from lineage- BM antigen presenting cells (C57 & BALB/c mice). Both MDSC subsets had potent capacity for in–vitro suppression of CD4+ and CD8+ T cells proliferation in response to anti-CD3/anti-CD28 beads and Con A. A ratio of 0.5/1 MDSC: T-cells were sufficient to inhibit >66% control levels of T-cell proliferation. MDSC isolated from transgenic mice that had been “knocked-out” for IFN-γ and IDO had equivalent suppressive activity as MDSC from wild-type donors. Addition of saturating concentrations of anti IL-10 and IL-4 MAb, or in combination with anti- IFN-γ MAb did not abrogate MDSC-suppressive activity. Ex-vivo culture of MDSC with mitogen-activated T-cells generated two—fold more Fox-p3 T-reg compared with cultures of T cell plus mitogen. Data will be presented regarding the novel role of MDSC involving in the homeostasis regulation of normal T-cell activation and proliferation in non-tumor-bearing mice. Disclosures: No relevant conflicts of interest to declare.

Induction of Indoleamine 2,3-Dioxygenase Expression by Interferon-g in Human Mesenchymal Stem Cells Inhibits Graft Versus Host Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4698-4698
Author(s):  
Myoung Woo Lee ◽  
Dae Seong Kim ◽  
Hye Jin Kim ◽  
Meong Hi Son ◽  
Soo Hyun Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
T Cell Proliferation ◽  
Activated T Cells ◽  
Graft Versus Host ◽  
Ifn Γ ◽  
Immunomodulatory Properties

Abstract Abstract 4698 Background: It is important to overcome the limitations such as graft rejection and graft versus host disease (GvHD) in allogeneic hematopoietic stem cell transplantation. Mesenchymal stem cells (MSCs), which evoke only minimal immune reactivity, may have anti-inflammatory and immunomodulatory effects. Purpose: In this study, we aimed to identify the immunomodulatory properties of human MSCs and to elucidate the possible mechanism of their properties for clinical treatment of allogeneic conflicts using MSCs. Materials & Methods: We conducted a comparative analysis about the immunomodulatory properties of MSCs derived from adult human tissues, including bone marrow (BM), adipose tissues (AT), umbilical cord blood (CB), and cord Wharton's jelly (WJ), in vitro and in vivo models. Results: AT-MSCs, CB-MSCs, and WJ-MSCs effectively suppressed phytohemagglutinin (PHA)-induced T-cell proliferation as effectively as did BM-MSCs. Levels of interferon (IFN)-g secreted from activated T-cells increased over time, but these levels were significantly reduced when cocultured with each type of MSCs. In addition, expression of indoleamine 2,3-dioxygenase (IDO) increased in MSCs treated with IFN-γ via JAK/STAT1 signaling pathways. Treatment with anti-IFN-g antibodies, JAK1/2 inhibitor or STAT1 siRNA restored PHA-induced T-cell proliferation. Use of an antagonist, 1-methyl-L-tryptophan, also restored PHA-induced T-cell proliferation, suggesting that IDO contributes to IFN-g-induced immunosuppression in MSCs. Moreover, infusion of IFN-g-treated MSCs decreased symptoms for human peripheral blood-derived mononuclear cells-induced GvHD in NOD/SCID mice, which resulted in an increase of survival rate of in vivo GvHD model. Conclusion: These data indicate that IFN-γ produced by activated T-cells is correlated with induction of IDO expression in MSCs by IFN-γ receptor/JAK/STAT1 pathway, which resulted in suppression of T-cell proliferation. Our findings suggest that MSCs derived from BM, AT, CB, or WJ could be used for clinical treatment of allogeneic conflicts. Disclosures: No relevant conflicts of interest to declare.

Endoplasmic reticulum stress induced Lox-1+ CD15+ polymorphonuclear myeloid-derived suppressor cells in hepatocellular carcinoma and associated with poor prognsis.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 38-38
Author(s):  
Xing Li ◽  
Xiang-yuan Wu ◽  
Nan Jiang ◽  
Yan-Fang Xing ◽  
Jie Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
T Cell ◽  
Binding Protein ◽  
Suppressor Cells ◽  
T Cell Proliferation ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Myeloid Derived Suppressor Cells ◽  
Ifn Γ

38 Background: A recent study indicated that Lectin-type oxidized LDL receptor-1 (LOX-1) was a distinct surface marker for human polymorphonuclears myeloid-derived suppressor cells (PMN-MDSC). The present study was aimed to investigate the existence LOX-1 PMN-MDSC in hepatocellular carcinoma (HCC) patients, the latent mechanism and their association with clinical parameters. Methods: 30 HCC patients and 30 health control were included. LOX-1+CD15+ PMN-MDSCs were investigated. Results: LOX-1+CD15+ PMN-MDSC were significantly elevated in both WB and PBMC of HCC patients compared with healthy control. LOX-1+CD15+ PMN-MDSC were more abundant in PBMC than WB. Addition of PMN-MDSCs resulted in significantly reduced proliferation and IFN-γ production of T cells with a dosage dependent manner. LOX-1-CD15+ PMNs present no suppressive function. The suppression on T cell proliferation and IFN-γ production was reversed by ROS inhibitor and Arginase inhibitor. ROS level of LOX-1+CD15+ PMN by DCFDA were higher in LOX-1+CD15+ PMN-MDSCs than LOX-1-CD15+ PMNs, as well as the mRNA levels of the NADPH oxidase NOX2. Meanwhile, the expression of arginase I and activity of arginase were also significantly raised in LOX-1+CD15+ PMN-MDSCs. LOX-1+CD15+ PMN-MDSCs displayed significantly higher expression of spliced X-box–binding protein 1 (sXBP1), ATF3 and CCAAT/enhancer binding protein (CHOP) were higher. For HCC patients, LOX-1+CD15+ PMN-MDSCs in WB were positively related to Cancer of the Liver Italian Program (CLIP) score. Conclusions: LOX-1+CD15+ PMN-MDSC were elevated in HCC patients and suppressed T cell proliferation through ROS/Arg I pathway with ER stress as a potential feature. LOX-1+CD15+ PMN-MDSC presented positive association with the prognosis of HCC patients.

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.

scholarly journals Compensation for Decreased Expression of B7 Molecules on Leishmania infantum-Infected Canine Macrophages Results in Restoration of Parasite-Specific T-Cell Proliferation and Gamma Interferon Production

1999 ◽  
Vol 67 (1) ◽  
pp. 237-243 ◽  
Author(s):  
Elena Pinelli ◽  
Victor P. M. G. Rutten ◽  
Martijn Bruysters ◽  
Peter F. Moore ◽  
E. Joost Ruitenberg
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Leishmania Infantum ◽  
Cell Activation ◽  
Gamma Interferon ◽  
T Cell Proliferation ◽  
B7 Molecules ◽  
Ifn Γ

ABSTRACT Infection of humans and dogs by Leishmania infantum may result in visceral leishmaniasis, which is characterized by impaired T-cell-mediated immune responses to parasite antigens. Dogs are natural hosts of Leishmania parasites and play an important role in the transmission of the parasites to humans. In an effort to characterize the immune response in dogs infected with this intracellular pathogen, we examined how infection with L. infantum affects canine macrophages and the consequences for T-cell activation in vitro. We showed that the proliferation of T-cell lines to cognate antigen decreases to background levels when infected autologous monocyte-derived macrophages are used as antigen-presenting cells (APC). The observed reduction of antigen-specific T-cell proliferation was shown to be dependent on the parasite load and to require cell-to-cell interaction of T cells with the infected APC. In addition, we observed a decreased expression of costimulatory B7 molecules on infected monocyte-derived macrophages. The expression of other surface molecules involved in T-cell activation, such as major histocompatibility complex class I and class II, on these cells did not change upon infection, whereas the expression of intracellular adhesion molecule 1 was marginally increased. Compensation for the decreased expression of B7 molecules by the addition of B7-transfected cells resulted in the restoration of cell proliferation and gamma interferon (IFN-γ) production by a Leishmania-specific T-cell line. These results showed that for the activation of parasite-specific canine T cells producing IFN-γ, which are most likely involved in protective immunity, sufficient expression of B7 molecules on infected macrophages is required. Provision of costimulatory molecules may be an approach for immunotherapy of leishmaniaisis as well as for vaccine development.

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