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  • Enhanced Dendritic Cell-Mediated Antigen-Specific CD4+ T Cell Responses: IFN-Gamma Aids TLR Stimulation

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    Author(s)
    Sheng, Kuo-Ching
    Day, Stephanie
    Wright, Mark D
    Stojanovska, Lily
    Apostolopoulos, Vasso
    Griffith University Author(s)
    Sheng, Kuo-Ching
    Year published
    2013
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    Abstract
    Phenotypic maturation and T cell stimulation are two functional attributes of DCs critical for immune induction. The combination of antigens, including those from cancer, with Toll-like receptor (TLR) ligands induces far superior cellular immune responses compared to antigen alone. In this study, IFN-gamma treatment of bone marrow-derived DC, followed by incubation with the TLR2, TLR4, or TLR9 agonists, enhanced DC activation compared to TLR ligation alone. Most notably, the upregulation of CD40 with LPS stimulation and CD86 with CpG stimulation was observed in in vitro cultures. Similarly, IFN-gamma coinjected with TLR ...
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    Phenotypic maturation and T cell stimulation are two functional attributes of DCs critical for immune induction. The combination of antigens, including those from cancer, with Toll-like receptor (TLR) ligands induces far superior cellular immune responses compared to antigen alone. In this study, IFN-gamma treatment of bone marrow-derived DC, followed by incubation with the TLR2, TLR4, or TLR9 agonists, enhanced DC activation compared to TLR ligation alone. Most notably, the upregulation of CD40 with LPS stimulation and CD86 with CpG stimulation was observed in in vitro cultures. Similarly, IFN-gamma coinjected with TLR ligands was able to promote DC activation in vivo, with DCs migrating from the site of immunization to the popliteal lymph nodes demonstrating increased expression of CD80 and CD86. The heightened DC activation translated to a drastic increase in T cell stimulatory capacity in both antigen independent and antigen dependent fashions. This is the first time that IFN-gamma has been shown to have a combined effect with TLR ligation to enhance DC activation and function. The results demonstrate the novel use of IFN-gamma together with TLR agonists to enhance antigen-specific T cell responses, for applications in the development of enhanced vaccines and drug targets against diseases including cancer.
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    Journal Title
    Journal of Drug Delivery
    Volume
    2013
    Issue
    516749
    DOI
    https://doi.org/10.1155/2013/516749
    Copyright Statement
    © The Author(s) 2013. The attached file is posted here with permission of the copyright owners for your personal use only. No further distribution permitted.For information about this journal please refer to the journal’s website. The online version of this work is licensed under a Creative Commons License, available at http://creativecommons.org/licenses/by-nc-sa/2.1/au/
    Subject
    Animal immunology
    Cellular immunology
    Publication URI
    http://hdl.handle.net/10072/55593
    Collection
    • Journal articles

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