DR5 activation of caspase-8 induces DC maturation and immune enhancement in vivo.
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.
Chattergoon
Michael A
MA
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Muthumani
Karuppiah
K
Tamura
Yutaka
Y
Ramanathan
Mathura
M
Shames
Jason P
JP
Saulino
Vera
V
Robinson
Tara M
TM
Montaner
Luis J
LJ
Weiner
David B
DB
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007114:Immunization / Q000379:methods; D020287:In Situ Nick-End Labeling; D009980:Influenza A virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000276:immunology*
D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053181:Caspase 8