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Journal of Virology, December 2009, p. 12027-12036, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.00593-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Persistence of Transgene Expression Influences CD8+ T-Cell Expansion and Maintenance following Immunization with Recombinant Adenovirus{triangledown}

Jonathan D. Finn,1 Jennifer Bassett,1 James B. Millar,1 Natalie Grinshtein,1 Teng Chih Yang,1 Robin Parsons,1 Carole Evelegh,1 Yonghong Wan,1 Robin J. Parks,2 and Jonathan L. Bramson1*

Center for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5,1 Ottawa Health Research Institute, 725 Parkdale Ave., Ottawa, Ontario, Canada K1Y 4E92

Received 23 March 2009/ Accepted 3 September 2009

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.

* Corresponding author. Mailing address: Department of Pathology and Molecular Medicine, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5. Phone: (905) 525-9140. Fax: (905) 522-6750. E-mail: bramsonj{at}mcmaster.ca

{triangledown} Published ahead of print on 16 September 2009.

Journal of Virology, December 2009, p. 12027-12036, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.00593-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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