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Journal of Drug Delivery
Volume 2013 (2013), Article ID 516749, 9 pages
http://dx.doi.org/10.1155/2013/516749
Research Article

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

1Immunology and Vaccine Laboratory, Burnet Institute, Melbourne, VIC 3004, Australia
2Institute for Glycomics, Griffith University, Gold Coast, QLD 4215, Australia
3Department of Immunology, Monash University, Melbourne, VIC 3004, Australia
4College of Health and Biomedicine, Victoria University, VIC 3021, Australia
5VA Consulting Services, Melbourne, VIC 3030, Australia

Received 12 December 2012; Accepted 18 February 2013

Academic Editor: Theresia Thalhammer

Copyright © 2013 Kuo-Ching Sheng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.