Variation in the immune response to adenoviral vectors in the brain: influence of mouse strain, environmental conditions and priming.
E1-deleted adenoviral vectors expressing the bacterial beta-galactosidase gene were inoculated into the brain of unprimed and primed C3H.He or C57BL/6J mice housed under either conventional or specific-pathogen-free (SPF) conditions. The kinetics of immune responses to both the vector and the transgene were investigated. In mice previously sensitized to adenovirus, the leukocyte infiltrate in the brain was dominated by CD8+ T cells, whereas in unprimed mice CD4+ T cells were present at higher levels. As expected, antibody titres to both adenovirus and beta-galactosidase were higher in primed mice than in unprimed mice after intracranial inoculation. C3H.He mice consistently made higher antibody responses than C57BL/6J mice. Although adenoviral vectors induced an inflammatory response under all conditions, mice housed in SPF facilities exhibited less inflammation than conventional mice and transgene expression persisted for longer. Irrespective of whether the mice had been deliberately primed to adenovirus, antibody titres were consistently lower in SPF mice compared with conventional mice. This study clearly demonstrates that environmental conditions, as well as previous priming to adenovirus, will affect both the quality and duration of the immune response triggered by gene delivery to the brain.
Ohmoto
Y
Y
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, UK.
Wood
M J
MJ
Charlton
H M
HM
Kajiwara
K
K
Perry
V H
VH
Wood
K J
KJ
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000276:immunology*; D007150:Immunohistochemistry; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors; D001616:beta-Galactosidase / Q000235:genetics
D001616:beta-Galactosidase