Dendritic cells transfected with cytopathic self-replicating RNA induce crosspriming of CD8+ T cells and antiviral immunity.
A potential shortcoming of nonlive vaccines is their relative inefficiency in generating T cell responses, thus limiting their application in infections requiring cellular immunity. Here, we present a system to induce cellular immunity and to study the immunological implications of time-delayed dendritic cell (DC) apoptosis and antigen reprocessing in vivo. We generated a self-replicating cytopathic pestivirus RNA to enhance production and presentation of hepatitis C virus (HCV) antigens and to induce apoptosis in DC 24-48 hr after transfection. Replicon-transfected H-2(b) DCs used to immunize HLA-A2 transgenic mice induced protection upon challenge with a vaccinia virus expressing HCV antigens. Induction of cell death enhanced the immunogenicity of DC-associated antigen. Transfer of cellular material from vaccine DCs to endogenous antigen presenting cells was visualized in lymph nodes and spleen, and crossprimed CD8(+) T cells were characterized. The findings are relevant for the rational design of vaccines against noncytopathic pathogens like HCV.
Racanelli
Vito
V
Liver Diseases Section, Digestive Diseases Branch, NIDDK, National Institutes of Health, DHHS, Bethesda, MD 20892, USA.
Behrens
Sven Erik
SE
Aliberti
Julio
J
Rehermann
Barbara
B
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D016174:Hepacivirus / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010576:Pestivirus / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014777:Virus Diseases / Q000276:immunology*
D012313:RNA