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.