Tolerogenic Antigen-Presenting Cells – Modulating Unwanted Immune Response at Their Core

2019 ◽  
Keyword(s):  
Immune Response ◽  
Antigen Presenting Cells ◽  
Antigen Presenting

The Hexavalent CD40 Agonist HERA-CD40L Induces T-Cell–mediated Antitumor Immune Response Through Activation of Antigen-presenting Cells

2018 ◽  
Vol 41 (9) ◽  
pp. 385-398 ◽  
Author(s):  
Christian Merz ◽  
Jaromir Sykora ◽  
Viola Marschall ◽  
David M. Richards ◽  
Karl Heinonen ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Antigen Presenting Cells ◽  
Antitumor Immune Response ◽  
Antigen Presenting

scholarly journals Cathepsin B in Antigen-Presenting Cells Controls Mediators of the Th1 Immune Response during Leishmania major Infection

2014 ◽  
Vol 8 (9) ◽  
pp. e3194 ◽  
Author(s):  
Iris J. Gonzalez-Leal ◽  
Bianca Röger ◽  
Angela Schwarz ◽  
Tanja Schirmeister ◽  
Thomas Reinheckel ◽  
...  
Keyword(s):  
Immune Response ◽  
Cathepsin B ◽  
Leishmania Major ◽  
Antigen Presenting Cells ◽  
Major Infection ◽  
Antigen Presenting ◽  
Th1 Immune Response

scholarly journals Sensitivity of Dendritic Cells to Microenvironment Signals

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Juliana Maria Motta ◽  
Vivian Mary Rumjanek
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Tumor Growth ◽  
Functional Status ◽  
Organ Transplantation ◽  
Immune Tolerance ◽  
Antigen Presenting Cells ◽  
Lessons Learned ◽  
Antigen Presenting ◽  
The Way

Dendritic cells are antigen-presenting cells capable of either activating the immune response or inducing and maintaining immune tolerance. They do this by integrating stimuli from the environment and changing their functional status as a result of plasticity. The modifications suffered by these cells have consequences in the way the organism may respond. In the present work two opposing situations known to affect dendritic cells are analyzed: tumor growth, leading to a microenvironment that favors the induction of a tolerogenic profile, and organ transplantation, which leads to a proinflammatory profile. Lessons learned from these situations may help to understand the mechanisms of modulation resulting not only from the above circumstances, but also from other pathologies.

Long-Term Phenotypic Correction of Hemophilia A Mice Following Intravenous Injection of miRNA-Regulated Lentiviral Vectors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2587-2587
Author(s):  
Hideto Matsui ◽  
Margareth Ozelo ◽  
Carol Hegadorn ◽  
Andrea Labelle ◽  
Erin Burnett ◽  
...  
Keyword(s):  
Immune Response ◽  
Intravenous Injection ◽  
Hemophilia A ◽  
Lentiviral Vector ◽  
Therapeutic Potential ◽  
Antigen Presenting Cells ◽  
Lentiviral Vectors ◽  
Target Sequence ◽  
Antigen Presenting

Abstract Hemophilia A is an excellent candidate disorder for the use of gene therapy as a treatment modality. To date, although lentiviral delivery of the factor VIII (FVIII) transgene has the potential to provide sustained therapeutic correction of the hemophilia A phenotype, this has not been achieved in adult animals because of the anti-FVIII immune response. We have used lentiviral vectors to deliver the canine FVIII transgene to hemophilia A neonates and although no anti-FVIII immune response occurred, and indeed the treated mice displayed long-term tolerance to the canine FVIII antigen, this strategy did not provide sustained therapeutic levels of plasma FVIII. To overcome these limitations, we modified our lentiviral vector and the protocol for viral delivery to enhance transduction of hepatocytes and direct transgene expression away from antigen presenting cells. We engineered lentiviral vectors that encode the B-domain deleted canine FVIII cDNA under the transcriptional control of either a non-viral ubiquitous promoter or two different liver-restricted promoters. However, no plasma FVIII was detected in any of the adult hemophilia A mice after intravenous injection of the various lentiviral vectors because of an anti-canine FVIII immune response. An alternate pseudotype (GP64) was used to enhance transduction of hepatocytes and a target sequence for a hematopoietic-specific microRNA was incorporated into the transgene to prevent FVIII expression in antigen presenting cells that may arise from promoter trapping. When hemophilia A mice received intravenous infusions of these modified vectors, where the cFVIII trangene is under the control of either of the liver-restricted promoters, all treated mice (n=4) showed sustained FVIII expression (mean FVIII levels 28.2±2.4 mU/mL) for more than 150 days (last time analyzed) without developing anti-FVIII antibodies. Moreover, temporary depletion of Kuppfer cells prior to viral administration resulted in a 3-fold elevation of levels of plasma FVIII (mean FVIII levels 83.3±2.1mU/mL; n=4). Analysis of the biodistribution of the integrated FVIII transgene and expression of canine FVIII mRNA indicate an enhanced restriction of FVIII expression in hepatocytes with the use of the modified lentiviral vectors. These results demonstrate, for the first time, the long-term therapeutic potential of modified lentiviral vectors for treating adult pre-clinical animal models of hemophilia A.

scholarly journals Selective Induction of Apoptosis in Antigen-Presenting Cells in Mice by Parapoxvirus ovis

2001 ◽  
Vol 75 (10) ◽  
pp. 4699-4704 ◽  
Author(s):  
Nicole Kruse ◽  
Olaf Weber
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Antigen Presenting Cells ◽  
T Cell Response ◽  
Survival Strategy ◽  
Short Intervals ◽  
Induction Of Apoptosis ◽  
Parapoxvirus Ovis ◽  
Antigen Presenting ◽  
Mouse System

ABSTRACT Viruses have evolved numerous mechanisms to avoid host immune reactions. Here we report a mechanism by which Parapoxvirus ovis (PPVO) interferes with antigen presentation. PPVO (orf virus) causes orf, an acute skin disease of sheep and goats worldwide. Importantly, PPVO can repeatedly infect its host in spite of a vigorous inflammatory and host immune response to the infection. We demonstrate in a mouse system that PPVO induces apoptosis in a significant number of antigen-presenting cells after intraperitoneal injection using the CD95 pathway, thus preventing a primary T-cell response. We also show that PPVO induces a compensatory activation of the immune system. Our results may help to explain the phenomenon that natural PPVO infections in sheep occur repeatedly even after short intervals. They also suggest that the combination of immunosuppressive and immunostimulatory mechanisms is an effective survival strategy that might be used in other viruses as well.

scholarly journals Humoral immune response in mice against a circulating antigen induced by adenoviral transfer is strictly dependent on expression in antigen-presenting cells

Blood ◽  
2003 ◽  
Vol 101 (7) ◽  
pp. 2551-2556 ◽  
Author(s):  
Bart R. De Geest ◽  
Sophie A. Van Linthout ◽  
Désiré Collen
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Time Course ◽  
Antigen Presenting Cells ◽  
Antigen Expression ◽  
Critical Determinant ◽  
Humoral Immune ◽  
Circulating Antigen ◽  
Adenoviral Transfer ◽  
Antigen Presenting

Adenoviral transfer of human apo A-I in Balb/c mice induces a strong humoral immune response against the transgene product when expression is driven from the ubiquitously active CMVpromoter but induces no immune response when driven by the hepatocyte-specific 256–base pair apo A-I promoter. Here the hypothesis was tested, which is that the humoral immune response against the circulating transgene product correlates with its expression in antigen-presenting cells. No humoral immune response was observed after adenoviral transfer of vectors with human apo A-I expression driven by the hepatocyte-specific apo C-II or 1.5-kilobase (kb) humanα1-antitrypsin promoter, but antibodies were induced after transfer with vectors driven by the ubiquitously activeU1b promoter and the murine MHCII Eβpromoter. A strict correlation was observed between antigen expression in the spleen and the occurrence of an immune response. Coinjection of the 1.5-kb human α1-antitrypsin and the murine MHCII Eβ promoter–driven vectors resulted in a very short-lived humoral immune response against human apo A-I, suggesting that the time course of human apo A-I expression is a critical determinant of the development of tolerance for human apo A-I. High titers of antibodies against human apo A-I after subcutaneous gene transfer with the MHCII Eβ promoter–driven vector underscore the potential of this promoter for vaccination purposes. In conclusion, humoral immune response in mice against a circulating antigen induced by adenoviral transfer is strictly dependent on expression in antigen-presenting cells.

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