Unexpectedly, induction of cytotoxic T lymphocytes enhances the humoral response after DNA immunization.

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.