Dong-Hoon Choi

Pohang University of Science and Technology, Andong, North Gyeongsang, South Korea

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Publications (4)15.71 Total impact

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    ABSTRACT: Chemokines have been known to play an important role in eliciting adaptive immune responses by, selectively attracting the innate cellular components to the site of antigen presentation. In this study, we demonstrated that all three CXCR3 ligands, CXCL9, CXCL10, and CXCL11, could act as a strong, genetic adjuvant. Among them, CXCL11 increased vaccine antigen-specific CD8 T cells, including, several cytokine secretions (IFN-γ and TNF-α) to a greater degree than the other two CXCR3 ligands. Fc-fusion of CXCL11 (CXCL11-Fc) induced similar but slightly higher CD8 T cell response, which, appeared to be antigen- (ovalbumin (OVA) vs. human papillomavirus 16 (HPV16) E7) and vaccine, type- (adenovirus vs. DNA vaccine) independent. In addition, the adjuvant effect of CXCL11-Fc was, further confirmed by suppressing tumor growth and extension of survival rates in a therapeutic tumor, model, which was correlated with enhanced antigen-specific CD8 T cell responses. Interestingly, the, enhanced antigen-specific CD8 T cell responses by co-delivery of CXCL11-Fc were associated with CD8, T cell proliferation, followed by increased total and effector memory T cell frequencies. Taken together, our findings provide a novel role of CXCL11 as a strong genetic adjuvant which might be used to, increase antigen-specific CD8 T cell immunity elicited by vaccination.
    Vaccine 08/2013; · 3.77 Impact Factor
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    ABSTRACT: Improvement to the immunogenicity of DNA vaccines was evaluated in a Mycobacterium tuberculosis (MTB) infection mouse model examining the combined effects of nonlytic Fc-fused IL-7 DNA (IL-7-nFc) and Flt3-ligand fused Mtb32 (F-Mtb32) DNA. Mice were treated with conventional chemotherapy for 6 weeks from 4 weeks after aerosol infection of MTB. Following the start of chemotherapy, DNA immunizations were administered five times with 2-week intervals. Coadministration of IL-7-nFc and F-Mtb32 DNA given during chemotherapy synergistically enhanced the magnitude of Mtb32-specific T cell responses and sustained for one-year after the last immunization assessed by IFN-γ ELISPOT assay. After dexamethasone treatment, a significantly reduced MTB reactivation was observed in mice received both IL-7-nFc and F-Mtb32 DNA, compared with F-MTb32 DNA alone or with control mice. In addition, mice treated with IL-7-nFc and F-Mtb32 DNA together showed improved lung pathology and reduced pulmonary inflammation values relative to F-Mtb32 DNA or saline injected mice. Intracellular cytokine staining revealed that the protection levels induced by combination therapy with IL-7-nFc and F-Mtb32 DNA was associated with enhanced Mtb32-specific IFN-γ secreting CD4(+) T cell responses and CD8(+) T cell responses stimulated with CTL epitope peptide in the lungs and spleens. These data suggest that IL-7-nFc as a novel TB adjuvant may facilitate therapeutic TB DNA vaccine to the clinics through significant enhancement of codelivered DNA vaccine-induced T cell immunity.
    Vaccine 04/2013; · 3.77 Impact Factor
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    ABSTRACT: Programmed death 1 (PD-1) signaling through its ligands, PD-L1 and PD-L2, has been known to negatively regulate T-cell responses. In addition, PD-L1 has been shown to interact with B7-1 costimulatory molecule to inhibit T-cell responses. Extensive studies have shown that PD-1/PD-L blockade restores exhausted T cells during chronic viral infections and tumors. In this study, we evaluated the effects of soluble PD-1 (sPD-1) as a blockade of PD-1 and PD-L1 on vaccine-elicited antigen-specific T-cell responses in mice. Coadministration of sPD-1 DNA with human papilloma virus-16 E7 DNA vaccine significantly enhanced E7-specific CD8(+) T-cell responses, resulting in potent antitumor effects against E7-expressing tumors. We also found that sPD-1, codelivered with adenovirus-based vaccine, could increase antigen-specific CD8(+) T-cell responses, indicating vaccine type-independent adjuvant effect of sPD-1. In addition, the frequency and functional activity of adoptively transferred OT-I cells, particularly memory CD8(+) T cells, were augmented by coadministration of sPD-1 DNA, which was closely associated with increased T-cell proliferation and reduced T-cell apoptosis through upregulation of Bcl-xL expression during T-cell activation. Codelivery of sPD-1 DNA also enhanced maturation of dendritic cells (DCs) in vivo which was accompanied by upregulation of DC maturation markers such as major histocompatibility complex class II. Taken together, our findings show that sPD-1 potently enhances codelivered antigen-specific CD8(+) T-cell responses and in vivo maturation of DCs during activation of naive CD8(+) T cells, suggesting that an immunization strategy with sPD-1 as an adjuvant can be used to increase antigen-specific T-cell immunity elicited by vaccination.
    Journal of immunotherapy (Hagerstown, Md.: 1997) 03/2011; 34(3):297-306. · 3.20 Impact Factor
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    ABSTRACT: IL-7 plays a crucial role in the homeostatic proliferation, differentiation and survival of T cells, as well as in the survival and proliferation of precursor B cells. Here, we demonstrated that utilizing nonlytic Fc-fused IL-7 (IL-7-Fc(m)) as a genetic adjuvant significantly enhanced not only CD4(+) but also CD8(+) T-cell responses by E7 DNA immunization, in addition to improving protection against TC-1-induced tumors in comparison to IL-7 alone. Similar results were obtained in OT-1 adoptive transfer experiments with OVA DNA injection, suggesting independence from antigenic nature and experimental conditions. In particular, the increased frequency of CD8(+) T cells was mainly due to enhanced T-cell proliferation in T-cell priming, and not to decreased cellular apoptosis. Interestingly, the enhanced adjuvant effect was not seen in the co-delivery of lytic Fc-fused IL-7 (IL-7-Fc) which increases T-cell apoptosis as well as T-cell proliferation, suggesting that the T-cell proliferative effect may be neutralized by T-cell apoptosis. Thus, our findings suggest that nonlytic Fc, in contrast to lytic Fc, fusion to cytokines may provide an insight in designing a potent genetic adjuvant for inducing CD4(+) and CD8(+) T-cell responses.
    European Journal of Immunology 11/2009; 40(2):351-8. · 4.97 Impact Factor