Persistence of transgene expression influences CD8+ T-cell expansion and maintenance following immunization with recombinant adenovirus.
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.
Finn
Jonathan D
JD
Department of Pathology and Molecular Medicine, McMaster University, Center for Gene Therapeutics, Hamilton, Ontario, Canada.
Bassett
Jennifer
J
Millar
James B
JB
Grinshtein
Natalie
N
Yang
Teng Chih
TC
Parsons
Robin
R
Evelegh
Carole
C
Wan
Yonghong
Y
Parks
Robin J
RJ
Bramson
Jonathan L
JL
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*
D014765:Viral Vaccines; D010047:Ovalbumin