RESUMO
Non-homeostatic tissue apoptosis in vivo has been shown to induce inflammatory responses and facilitate the cross-presentation of proteins within apoptotic bodies. We hypothesize that in the presence of foreign antigens, the apoptotic-inflammatory process improves immune priming; further, molecules that trigger apoptosis may be adapted for use as immune adjuvants. One very attractive molecule in this context is the tumor necrosis factor receptor (TNFR) family molecule DR5/TRAIL-receptor 2. We show a significant improvement in CD8(+) T-cell mediated vaccine immunity with the use of death receptor-5 (DR5) as an immune adjuvant, a property that is correlated with the activation of caspases-8 (casp8) and dependent on its ability to induce apoptosis in vivo.
Assuntos
Caspase 8/metabolismo , Células Dendríticas/imunologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/imunologia , Animais , Apoptose/genética , Apoptose/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Proliferação de Células , Células Dendríticas/metabolismo , Feminino , Citometria de Fluxo , Imunização/métodos , Marcação In Situ das Extremidades Cortadas , Vírus da Influenza A/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genéticaRESUMO
Plasmid encoded exogenous IL-12 delivered as a DNA vaccine adjuvant has been shown to improve vaccine-induced immunity. In particular, pIL-12 greatly improves antigen (Ag)-specific cytotoxic tlymphocyte (CTL) activity in immunized mice. The longevity of this response has not previously been studied in detail. We have studied the effect of co-immunization with pIL-12 on HIV gp160 and Influenza A Hemeagglutinnin-specific memory immune responses. Mice co-immunized with pIL-12 and plasmid encoded antigens maintained a greater memory response than those immunized with the plasmid antigen alone which could be measured at least 6 months after vaccination. Further, this translated to an improved outcome after challenge of long term rested mice that were previously immunized. The strength of the immune response as well as the number of Ag-specific T-cells is proportional to the number of Ag-specific cells primed by the vaccination regimen.