title: Unexpectedly, induction of cytotoxic T lymphocytes enhances the humoral response after DNA immunization.
abstract: Although there are many examples (eg, immune deviation) in which enhanced cellular responses correspond with lower humoral responses, here we demonstrate for the first time 2 models in which cytotoxic T-lymphocyte (CTL) activity is associated with an enhanced antibody response. First, C57BL/6 mice generate a stronger antibody response to ovalbumin DNA immunization than congenic bm1 mice. The latter differ from C57BL/6 mice in that the H-2Kb molecule is mutated so that the immunodominant CTL epitope of ovalbumin is no longer presented. Second, pre-existing CTLs (induced by ovalbumin peptide-priming) increased the antibody response to a second unrelated antigen (beta-galactosidase) co-immunized with ovalbumin. One possible mechanism is that CTLs may release antigen from DNA-transfected cells by killing or damaging them, and this freed antigen is then accessible to dendritic cells and B cells. Our finding of CTL-mediated antibody enhancement has important implications for tumor and viral immunobiology and vaccination.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dyer
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhan
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Brady
authors.forename: Francis R
authors.initials: FR
authors.lastname: Carbone
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lew
mesh_terms: D000818:Animals; D000917:Antibody Formation; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D007114:Immunization; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000939:Epitopes; D019444:Vaccines, DNA; D010047:Ovalbumin