title: Co-immunisation with DNA encoding RANK/RANKL or 4-1BBL costimulatory molecules does not enhance effector or memory CTL responses afforded by immunisation with a tumour antigen-encoding DNA vaccine.
abstract: T cell mediated immune responses are induced following interaction of MHC-presented epitope on professional antigen presenting cells such as dendritic cells (DCs) with cognate T cell receptor. Up-regulation of receptor-ligand pairs of costimulatory molecules linking DC to T cell enhances the resulting T cell responses. This 'second signalling' occurs through the B7 molecules CD80/86 expressed by DCs, and importantly through members of the TNF ligand/TNF receptor superfamilies. We have previously shown that co-expression of RANK/RANKL or 41BB-L in addition to tumour antigen in dendritic cells augmented cognate effector and memory tumour antigen-directed cytotoxic T cell responses when the DCs were used to immunise mice. Here, we examined whether co-immunisation with naked plasmid DNAs encoding antigen and these costimulatory molecule(s), would enhance antigen specific T cell responses. We demonstrate that co-immunisation with DNAs encoding tumour antigen and costimulatory molecules failed to enhance antigen-directed CTL responses, or tumour protection, afforded by immunisation with DNA encoding tumour antigen alone.
authors.affiliation: Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Brisbane, Australia.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Herd
authors.forename: Carsten
authors.initials: C
authors.lastname: Wiethe
authors.forename: Robert W
authors.initials: RW
authors.lastname: Tindle
mesh_terms: D053330:4-1BB Ligand / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004247:DNA / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007114:Immunization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D053330:4-1BB Ligand; D000951:Antigens, Neoplasm; D011506:Proteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D019444:Vaccines, DNA; D049452:Green Fluorescent Proteins; D004247:DNA