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Journal of Virology, December 2000, p. 11690-11696, Vol. 74, No. 24
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Profound Protection against Respiratory Challenge with a Lethal H7N7 Influenza A Virus by Increasing the Magnitude of CD8+ T-Cell Memory

Jan P. Christensen,dagger Peter C. Doherty,* Kristen C. Branum,dagger and Janice M. Riberdy

Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105

Received 15 May 2000/Accepted 26 September 2000

The recall of CD8+ T-cell memory established by infecting H-2b mice with an H1N1 influenza A virus provided a measure of protection against an extremely virulent H7N7 virus. The numbers of CD8+ effector and memory T cells specific for the shared, immunodominant DbNP366 epitope were greatly increased subsequent to the H7N7 challenge, and though lung titers remained as high as those in naive controls for 5 days or more, the virus was cleared more rapidly. Expanding the CD8+ memory T-cell pool (<0.5 to >10%) by sequential priming with two different influenza A viruses (H3N2right-arrowH1N1) gave much better protection. Though the H7N7 virus initially grew to equivalent titers in the lungs of naive and double-primed mice, the replicative phase was substantially controlled within 3 days. This tertiary H7N7 challenge caused little increase in the magnitude of the CD8+ DbNP366+ T-cell pool, and only a portion of the memory population in the lymphoid tissue could be shown to proliferate. The great majority of the CD8+ DbNP366+ set that localized to the infected respiratory tract had, however, cycled at least once, though recent cell division was shown not to be a prerequisite for T-cell extravasation. The selective induction of CD8+ T-cell memory can thus greatly limit the damage caused by a virulent influenza A virus, with the extent of protection being directly related to the number of available responders. Furthermore, a large pool of CD8+ memory T cells may be only partially utilized to deal with a potentially lethal influenza infection.

* Corresponding author. Mailing address: Department of Immunology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105. Phone: (901) 495-3470. Fax: (901) 495-3107. E-mail: peter.doherty{at}stjude.org.

dagger Present address: Department of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark.

Journal of Virology, December 2000, p. 11690-11696, Vol. 74, No. 24
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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