Dendritic Cells Transfected with Cytopathic Self-Replicating RNA Induce Crosspriming of CD8⁺ T cells and Antiviral Immunity

Speaker: 黃文彥

Commentator: 蕭璦莉  老師

Date: 2004/3/10, 15:00~16:00

Place: Room 601

Abstract:

    The poor T cell responses induced by non-viable antigens are the major problem for developing vaccines for pathogens and cancers.  Dendritic cells (DCs) are known to play an important role in inducing and regulating adaptive immune responses.¹  They capture antigens in the peripheral tissues and migrate to secondary lymphoid organs where they prime naïve T cells.²  Because of these unique abilities of DCs, they are thought to be potent antigen vehicles for vaccination.  In this paper, the authors created a system that they transfected DCs with cytopathic self-replicating RNA in order to investigate the cellular antigens reprocessing and the immune responses.  The DCs were apoptosis in cell culture 1 or 2 days after transfecting with pestivirus replicon expressing hepatitis C virus (HCV) antigen.  The authors also subcutaneously injected the transfected mouse DCs into the HLA-A2-transgenic mice that had been already adoptive transferred with H-2^b cells.  They found that the antigen presenting cells in the secondary lymphoid organs internalized the cellular fragments of DCs.  They also discovered that both the H-2^b and HLA-A2 restricted T cells were primed and cross-primed, respectively.  Immunizing the mice with these DCs expressing HCV nonstructural protein 3 can induce both specific CD8⁺ and CD4⁺ T cell responses and protect the mice from virus infection.  These findings suggest a new vaccine strategy to overcome the poor T cell responses induced by non-cytopathic pathogens such as HCV.³

References:

1.     Banchereau, J., and R. M. Steinman. 1998. Dendritic cells and control of immunity. Nature 392: 245-252.

2.     Guermonprez, P., J. Valladeau, L. Zitvogel, C. Thery, and S. Amingorena. 2002. Antigen presentation and T cell stimulation by dendritic cells. Annu. Rev. Immunol. 20: 621-667.

3.     Racanelli, V., S. E. Behrens, J. Aliberti, and B. Rehermann. 2004. Dendritic cells transfected with cytopathic self-replicating RNA induce crosspriming of CD8⁺ T cells and antiviral immunity. Immunity 20: 47-58.