Abstract
Induced pluripotent stem cells (iPSCs) are artificially derived from somatic cells that have been transduced with defined reprogramming factors. A previous report has indicated the possibility of using iPSCs as an immune stimulator to generate antigen-specific immunity. In our current study, we have investigated whether human iPSCs (hiPSCs) have the ability to enhance specific immune response against a human immunodeficiency virus type 1 (HIV-1) antigen in a xenogenic mouse model. Our results show that BALB/c mice immunized with hiPSCs transduced with an adenoviral vector encoding HIV-1 gp160 exhibited prominent antigen-specific cellular immune responses. We further found that pre-treatment of hiPSCs with ionizing radiation promotes the secretion of pro-inflammatory cytokines such as interleukin-1 alpha (IL-1α), IL-12, and IL-18. These cytokines might promote the activation of antigen-presenting cells and the effective induction of cellular immunity. Our present findings thus demonstrate that a hiPSCs-based vaccine has the potential to generate cellular immunity against viral antigens such as HIV-1 gp160 in a xenogenic condition.
Highlights
The latest estimate indicates that 33.4 million people are living with human immunodeficiency virus (HIV)/AIDS in 2009, and there are some 2.7 million new infections each year
RT-PCR analysis revealed that the Induced pluripotent stem cells (iPSCs) markers Oct4, Nanog, and hTERT were strongly expressed in the cells before and after the transduction of HIV type 1 (HIV-1) gp160, but this was not the case in MRC5 fibroblasts (Figure 1C)
Immunization with human induced pluripotent stem cell (hiPSC) and the immune responses generated We investigated whether hiPSCs could induce cellular immune response against the viral antigen in a mouse model
Summary
The latest estimate indicates that 33.4 million people are living with human immunodeficiency virus (HIV)/AIDS in 2009, and there are some 2.7 million new infections each year. The development of a safe and effective HIV/AIDS vaccine is required urgently to halt this epidemic. Current approaches in the development of HIV/AIDS vaccines have focused not on preventing infection itself, but on eliciting potent antiviral-specific CD8+ T cell [cytotoxic T lymphocyte (CTL)] responses to limit viral replication (Yamamoto and Matano, 2008). This is in part because such an immune response contributes to non-progression of AIDS in people infected with HIV type 1 (HIV-1). It is desirable to develop a new vaccine vector system for generating effective CTL response against HIV-1
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