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

Sheng, KC, Day, S, Wright, MD, Stojanovska, Lily and Apostolopoulos, Vasso ORCID: 0000-0001-6788-2771 (2013) Enhanced Dendritic Cell-Mediated Antigen-Specific CD4+ T Cell Responses: IFN-Gamma Aids TLR Stimulation. Journal of drug delivery, 2013. ISSN 2090-3014

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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 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.

Item Type: Article
Additional Information:

Article ID 516749

Uncontrolled Keywords: DC
Subjects: FOR Classification > 1199 Other Medical and Health Sciences
Faculty/School/Research Centre/Department > College of Health and Biomedicine
Depositing User: Symplectic Elements
Date Deposited: 10 Jun 2015 00:37
Last Modified: 03 Apr 2019 01:51
URI: http://vuir.vu.edu.au/id/eprint/26751
DOI: https://doi.org/10.1155/2013/516749
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