title: Persistence of transgene expression influences CD8+ T-cell expansion and maintenance following immunization with recombinant adenovirus.
abstract: Previous studies determined that the CD8(+) T-cell response elicited by recombinant adenovirus exhibited a protracted contraction phase that was associated with long-term presentation of antigen. To gain further insight into this process, a doxycycline-regulated adenovirus was constructed to enable controlled extinction of transgene expression in vivo. We investigated the impact of premature termination of transgene expression at various time points (day 3 to day 60) following immunization. When transgene expression was terminated before the maximum response had been attained, overall expansion was attenuated, yielding a small memory population. When transgene expression was terminated between day 13 and day 30, the memory population was not sustained, demonstrating that the early memory population was antigen dependent. Extinction of transgene expression at day 60 had no obvious impact on memory maintenance, indicating that maintenance of the memory population may ultimately become independent of transgene expression. Premature termination of antigen expression had significant but modest effects on the phenotype and cytokine profile of the memory population. These results offer new insights into the mechanisms of memory CD8(+) T-cell maintenance following immunization with a recombinant adenovirus.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Center for Gene Therapeutics, Hamilton, Ontario, Canada.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Finn
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bassett
authors.forename: James B
authors.initials: JB
authors.lastname: Millar
authors.forename: Natalie
authors.initials: N
authors.lastname: Grinshtein
authors.forename: Teng Chih
authors.initials: TC
authors.lastname: Yang
authors.forename: Robin
authors.initials: R
authors.lastname: Parsons
authors.forename: Carole
authors.initials: C
authors.lastname: Evelegh
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Wan
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Parks
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Bramson
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D014765:Viral Vaccines; D010047:Ovalbumin