Galectin-1 Confers Endometrial Gene Expression and Protein Related to Maternal-Conceptus Immune Tolerance in Cattle

2021 ◽  
Author(s):  
Heather L Chaney ◽  
Lindsay F Grose ◽  
Jeanna M LaBarbara ◽  
Adam W Sirk ◽  
Alyssa M Blancke ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Dendritic Cells ◽  
Estrous Cycle ◽  
Immune Tolerance ◽  
Immune Suppression ◽  
Carbohydrate Binding ◽  
Expression Of Genes ◽  
Pregnant Sheep ◽  
Carbohydrate Binding Proteins

Abstract Conceptus secretory factors include galectins, a family of carbohydrate binding proteins that elicit cell adhesion and immune suppression by interacting with intracellular and extracellular glycans. In rodents, galectin-1 (LGALS1) promotes maternal-fetal immune tolerance in the decidua through expansion of tolerogenic CD11c+ dendritic cells, increased anti-inflammatory IL-10, and activation of FOXP3+ regulatory T cells (Treg). This study characterized galectin expression in early ruminant conceptuses and endometrium. We also tested the effect of recombinant bovine LGALS1 (rbLGALS1) and progesterone (P4) on endometrial expression of genes and protein related to maternal-fetal immune tolerance in cattle. Elongating bovine and ovine conceptuses expressed several galectins, particularly, LGALS1, LGALS3 and LGALS8. Within bovine endometrium, expression of LGALS3, LGALS7 and LGALS9 was greater on Day 16 of pregnancy compared to the estrous cycle. Within ovine endometrium, LGALS7 was greater during pregnancy compared to the estrous cycle and endometrium of pregnant sheep tended to have greater LGALS9 and LGALS15. Expression of endometrial LGALS4 was less during pregnancy in sheep. Treating bovine endometrium with rbLGALS1 increased endometrial expression of CD11c, IL-10 and FOXP3, within 24 h. Specifically, within caruncular endometrium, both rbLGALS1 and P4 increased FOXP3, suggesting that both ligands may promote Treg expansion. Using IHC, FOXP3+ cells with a leukocyte phenotype were localized to the bovine uterine stratum compactum near the uterine surface and increased in response to rbLGALS1. We hypothesize that galectins have important functions during establishment of pregnancy in ruminants and bovine conceptus LGALS1 and luteal P4 confer mechanisms of maternal-conceptus immune tolerance in cattle.

scholarly journals Tolerogenic nanoparticles restore the antitumor activity of recombinant immunotoxins by mitigating immunogenicity

2018 ◽  
Vol 115 (4) ◽  
pp. E733-E742 ◽  
Author(s):  
Ronit Mazor ◽  
Emily M. King ◽  
Masanori Onda ◽  
Nicolas Cuburu ◽  
Selamawit Addissie ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Monoclonal Antibodies ◽  
Antitumor Activity ◽  
Regulatory T Cells ◽  
Immune Tolerance ◽  
Checkpoint Inhibitors ◽  
Recombinant Immunotoxins ◽  
Antidrug Antibodies

Protein-based drugs are very active in treating cancer, but their efficacy can be limited by the formation of neutralizing antidrug antibodies (ADAs). Recombinant immunotoxins are proteins that are very effective in patients with leukemia, where immunity is suppressed, but induce ADAs, which compromise their activity, in patients with intact immunity. Here we induced a specific, durable, and transferable immune tolerance to recombinant immunotoxins by combining them with nanoparticles containing rapamycin (SVP-R). SVP-R mitigated the formation of inhibitory ADAs in naïve and sensitized mice, resulting in restoration of antitumor activity. The immune tolerance is mediated by colocalization of the SVP-R and immunotoxin to dendritic cells and macrophages in the spleen and is abrogated by depletion of regulatory T cells. Tolerance induced by SVPs was not blocked by checkpoint inhibitors or costimulatory agonist monoclonal antibodies that by themselves enhance ADA formation.

Interleukin-12 Gene Expression into Acute Myeloid Leukemia-Derived Dendritic Cells Overcomes T-Cell Functional Impairment Induced by Leukemic Microenvironment.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1816-1816
Author(s):  
Antonio Curti ◽  
Simona Pandolfi ◽  
Michela Aluigi ◽  
Alessandro Isidori ◽  
Isabella Alessandrini ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Dendritic Cells ◽  
T Cell ◽  
Myeloid Leukemia ◽  
Interleukin 12 ◽  
Functional Features ◽  
Ifn Γ ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) cells are poorly immunogenic and release soluble factors inhibiting T-cell function. AML-derived dendritic cells (AML-DCs) have better antigen presentation capacity than leukemic blasts but share with AML cells some immunosuppressive features. In this study, we show that AML-DCs generated from CD14− AML samples (which represent 80% of total AML patients) are defective in IL-12 production. We, then, transfected CD14−-derived AML-DCs with IL-12 gene through the novel non-viral method nucleofection. IL-12 gene-nucleofected AML-DCs produce significant amount of IL-12 while maintain leukemia-specific karyotype, DC-like phenotype and function. In presence of the supernatant from the human leukemic cell line K562, allogeneic T-cell proliferation and interferon (IFN)-γ production induced by mock-transduced AML-DCs are significantly reduced. This effect is mainly directed on T cells, since AML-DC phenotype and cytokine production are not affected by leukemic supernatant. However, when stimulated by IL-12-producing AML-DCs, T cells produce higher concentrations of IFN-γ, thus maintaining a Th1 cytokine profile. In conclusion, IL-12 gene can be expressed into AML-DCs defective in endogenous IL-12 production by using a novel non-viral method which does not modify their phenotypical, cytogenetic and functional features. IL-12 gene expression into AML-DC counteracts the inhibitory effect of leukemic microenvironment on T lymphocytes

Immune Suppression by γδ T-cells as a Potential Regulatory Mechanism After Cancer Vaccination With IL-12 Secreting Dendritic Cells

2010 ◽  
Vol 33 (1) ◽  
pp. 40-52 ◽  
Author(s):  
Michael W. Traxlmayr ◽  
Daniela Wesch ◽  
Alexander M. Dohnal ◽  
Philipp Funovics ◽  
Michael B. Fischer ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Suppression ◽  
Regulatory Mechanism ◽  
Γδ T Cells ◽  
Cancer Vaccination ◽  
After Cancer

scholarly journals Dendritic cells transduced with TIPE-2 recombinant adenovirus induces T cells suppression

2020 ◽  
Author(s):  
Shudong Liu ◽  
jie wang ◽  
Wenyan Li ◽  
Hui Shi ◽  
Changlong Zhou ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Suppression ◽  
Cytokine Production ◽  
Recombinant Adenovirus ◽  
Inflammatory Diseases ◽  
Cd8 T Cell ◽  
Negative Regulator ◽  
Activation Marker

Abstract Introduction: TIPE-2 has been identified as a negative regulator of both innate and adaptive immunity and is involved in several inflammatory diseases. However, the role of immune suppression of dendritic cells (DCs) transduced with TIPE-2 has not been well studied. Methods: In this study, DCs were transduced with TIPE-2 recombinant adenovirus, and then were cocultured with allogeneic CD4+ or CD8+T cells. The proliferation, cytokine production and activation marker levels of CD4+ or CD8+T cell were detected. Results: The data demonstrated that T cell proliferation, cytokine production and activation marker levels were attenuated after treated with TIPE-2 transduced DCs. Conclusions: These results suggested that TIPE-2 transduced DCs are capable of inducing allogeneic CD4+ or CD8+T cell immune suppression, which provide a promising way for the therapeutical strategies of transplantation or autoimmune diseases.

scholarly journals Sirtuin1 Targeting Reverses Innate and Adaptive Immune Tolerance in Septic Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Ayana N. Martin ◽  
Martha Alexander-Miller ◽  
Barbara K. Yoza ◽  
Vidula Vachharajani ◽  
Charles E. McCall
Keyword(s):  
T Cells ◽  
Immune Tolerance ◽  
Cd8 T Cells ◽  
Immune Suppression ◽  
Glucose Oxidation ◽  
Viral Infections ◽  
Selective Inhibitor ◽  
Survival Strategies ◽  
Adaptive Immune ◽  
Specific Tolerance

Resistance and tolerance to infection are two universal fitness and survival strategies used by inflammation and immunity in organisms and cells to guard homeostasis. During sepsis, however, both strategies fail, and animal and human victims often die from combined innate and adaptive immune suppression with persistent bacterial and viral infections. NAD+-sensing nuclear sirtuin1 (SIRT1) epigenetically guards immune and metabolic homeostasis during sepsis. Pharmacologically inhibiting SIRT1 deacetylase activity in septic mice reverses monocyte immune tolerance, clears infection, rebalances glycolysis and glucose oxidation, resolves organ dysfunction, and prevents most septic deaths. Whether SIRT1 inhibition during sepsis treatment concomitantly reverses innate and T cell antigen-specific immune tolerance is unknown. Here, we show that treating septic mice with a SIRT1 selective inhibitor concordantly reverses immune tolerance splenic dendritic and antigen-specific tolerance of splenic CD4+ and CD8+ T cells. SIRT1 inhibition also increases the ratio of IL12 p40+ and TNFα proinflammatory/immune to IL10 and TGFβ anti-inflammatory/immune cytokines and decreases the ratio of CD4+ TReg repressor to CD4+ activator T cells. These findings support the unifying concept that nuclear NAD+ sensor SIRT1 broadly coordinates innate and adaptive immune reprogramming during sepsis and is a druggable immunometabolic enhancement target.

scholarly journals Predominant Role for Directly Transfected Dendritic Cells in Antigen Presentation to CD8+ T Cells after Gene Gun Immunization

1998 ◽  
Vol 188 (6) ◽  
pp. 1075-1082 ◽  
Author(s):  
Angel Porgador ◽  
Kari R. Irvine ◽  
Akiko Iwasaki ◽  
Brian H. Barber ◽  
Nicholas P. Restifo ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Antigen Presentation ◽  
Cd8 T Cells ◽  
Cytotoxic T Cell ◽  
Gene Gun ◽  
Cross Presentation

Cutaneous gene (DNA) bombardment results in substantial expression of the encoded antigen in the epidermal layer as well as detectable expression in dendritic cells (DC) in draining lymph nodes (LNs). Under these conditions, two possible modes of DC antigen presentation to naive CD8+ T cells might exist: (a) presentation directly by gene-transfected DC trafficking to local lymph nodes, and (b) cross-presentation by untransfected DC of antigen released from or associated with transfected epidermal cells. The relative contributions of these distinct modes of antigen presentation to priming for cytotoxic T cell (CTL) responses have not been clearly established. Here we show that LN cells directly expressing the DNA-encoded antigen are rare; 24 h after five abdominal skin bombardments, the number of these cells does not exceed 50–100 cells in an individual draining LN. However, over this same time period, the total number of CD11c+ DC increases more than twofold, by an average of 20,000–30,000 DC per major draining node. This augmentation is due to gold bombardment and is independent of the presence of plasmid DNA. Most antigen-bearing cells in the LNs draining the site of DNA delivery appear to be DC and can be depleted by antibodies to an intact surface protein encoded by cotransfected DNA. This finding of predominant antigen presentation by directly transfected cells is also consistent with data from studies on cotransfection with antigen and CD86-encoding DNA, showing that priming of anti-mutant influenza nucleoprotein CTLs with a single immunization is dependent upon coexpression of the DNAs encoding nucleoprotein and B7.2 in the same cells. These observations provide insight into the relative roles of direct gene expression and cross-presentation in CD8+ T cell priming using gene gun immunization, and indicate that augmentation of direct DC gene expression may enhance such priming.

scholarly journals Immune Tolerance After Delivery of Dying Cells to Dendritic Cells In Situ

2002 ◽  
Vol 196 (8) ◽  
pp. 1091-1097 ◽  
Author(s):  
Kang Liu ◽  
Tomonori Iyoda ◽  
Marzena Saternus ◽  
Yukino Kimura ◽  
Kayo Inaba ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Steady State ◽  
Immune Tolerance ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Interferon Γ ◽  
Presentation Of Self ◽  
Dying Cells

Peripheral immune tolerance is believed to be induced by the processing and presentation of self-tissues that die during physiologic tissue turnover. To examine the mechanism that mediates tolerance, we injected mice with dying syngeneic TAP−/− splenocytes loaded with small amounts of the protein antigen, ovalbumin (OVA). After ingestion and presentation of cell-associated OVA by the CD8+ subset of dendritic cells in situ, large numbers of antigen-reactive, CD8+ T cell receptor (TCR) transgenic T lymphocytes were driven into cell cycle, but then the T cells were deleted. The animals were also tolerant to challenge with OVA in complete Freund's adjuvant. An agonistic anti-CD40 monoclonal antibody was then administered together with the OVA-loaded splenocytes, so that the dendritic cells in the recipient mice would mature. In contrast to observations made in the steady state, the antigen-reactive T cells expanded in numbers for 1–2 wk and produced large amounts of interleukin 2 and interferon γ, while the animals retained responsiveness to antigen rechallenge. The specific tolerance that develops when dendritic cells process self tissues in the steady state should prevent or reduce the development of autoimmunity when dying cells are subsequently processed during infection.

25: Infiltration of ovarian cancer by functional regulatory T cells and altered plasmacytoid dendritic cells could contribute to local immune tolerance

2010 ◽  
Vol 97 (1) ◽  
pp. S25
Author(s):  
Bendriss-Vermare Nathalie ◽  
Intidhar Labidi-Galy ◽  
Isabelle Ray-Coquard ◽  
Vanja Sisirak ◽  
Julien Faget ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Dendritic Cells ◽  
Regulatory T Cells ◽  
Immune Tolerance ◽  
Plasmacytoid Dendritic Cells

scholarly journals Antitumor Effect of KML-B-Treated Dendritic Cells via Induction of Lymphocyte Activation

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Jong-Jin Kim ◽  
Yun-Ho Hwang ◽  
Kyung-Yun Kang ◽  
Sung-Ju Lee ◽  
Jong-Bae Kim ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Antitumor Effect ◽  
Biological Activities ◽  
Lymphocyte Activation ◽  
Carbohydrate Binding ◽  
Mistletoe Lectin

Lectins are carbohydrate-binding proteins with various biological activities, such as antitumor and immunomodulatory effects. Although lectins have various biological activities, they are still limited by cytotoxicity in normal cells. To overcome this problem, we used the noncytotoxic part of Korean mistletoe lectin B-chain (KML-B) to induce maturation of dendritic cells (DCs). A previous study reported that KML-B induces DC maturation by triggering TLR-4, including expression of costimulatory molecules (CD40, CD80, and CD86), MHC II, and secretion of cytokines in DCs. Additionally, matured DCs by KML-B induced T helper (Th) cell activation and differentiation toward Th1 cells. However, the interaction of KML-B-treated DCs with CD8+ T cells is still poorly understood. In this study, we confirmed the ability of matured DCs by KML-B to stimulate cytotoxic T cells using OT-1 mouse-derived CD8+ T cells. KML-B induced MHC I expression in DCs, stimulation of CD8+ T cell activation and proliferation, and IFN-γ secretion. Moreover, tumor sizes were reduced by KML-B treatment during vaccination of OVA257−264-pulsed DCs. Here, we confirmed induction of CD8+ T cell activation and the antitumor effect of KML-B treatment in DCs.

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