scholarly journals A Schistosome-Expressed Immunomodulatory Glycoconjugate Expands Peritoneal Gr1+Macrophages That Suppress Naive CD4+T Cell Proliferation Via an IFN-γ and Nitric Oxide-Dependent Mechanism

2001 ◽  
Vol 167 (8) ◽  
pp. 4293-4302 ◽  
Author(s):  
Olga Atochina ◽  
Toby Daly-Engel ◽  
Danuta Piskorska ◽  
Edward McGuire ◽  
Donald A. Harn
Keyword(s):  
Nitric Oxide ◽  
Cell Proliferation ◽  
T Cell ◽  
Cd4 T Cell ◽  
T Cell Proliferation ◽  
Ifn Γ ◽  
Dependent Mechanism

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

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 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.

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

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 Inflammation-induced inhibition of chaperone-mediated autophagy maintains the immunosuppressive function of murine mesenchymal stromal cells

2020 ◽  
Author(s):  
Jie Zhang ◽  
Jiefang Huang ◽  
Yuting Gu ◽  
Mingxing Xue ◽  
Fengtao Qian ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Proliferation ◽  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Inflammatory Cells ◽  
T Cell Proliferation ◽  
Tnf Α ◽  
Ifn Γ ◽  
Chaperone Mediated Autophagy

AbstractMacroautophagy has been implicated in modulating the therapeutic function of mesenchymal stromal cells (MSCs). However, the biological function of chaperone-mediated autophagy (CMA) in MSCs remains elusive. Here, we found that CMA was inhibited in MSCs in response to the proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). In addition, suppression of CMA by knocking down the CMA-related lysosomal receptor lysosomal-associated membrane protein 2 (LAMP-2A) in MSCs significantly enhanced the immunosuppressive effect of MSCs on T cell proliferation, and as expected, LAMP-2A overexpression in MSCs exerted the opposite effect on T cell proliferation. This effect of CMA on the immunosuppressive function of MSCs was attributed to its negative regulation of the expression of chemokine C-X-C motif ligand 10 (CXCL10), which recruits inflammatory cells, especially T cells, to MSCs, and inducible nitric oxide synthase (iNOS), which leads to the subsequent inhibition of T cell proliferation via nitric oxide (NO). Mechanistically, CMA inhibition dramatically promoted IFN-γ plus TNF-α-induced activation of NF-κB and STAT1, leading to the enhanced expression of CXCL10 and iNOS in MSCs. Furthermore, we found that IFN-γ plus TNF-α-induced AKT activation contributed to CMA inhibition in MSCs. More interestingly, CMA-deficient MSCs exhibited improved therapeutic efficacy in inflammatory liver injury. Taken together, our findings established CMA inhibition as a critical contributor to the immunosuppressive function of MSCs induced by inflammatory cytokines and highlighted a previously unknown function of CMA.

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
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