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Journal of Virology, July 2003, p. 7756-7763, Vol. 77, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.14.7756-7763.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Quantitative Analysis of Long-Term Virus-Specific CD8+-T-Cell Memory in Mice Challenged with Unrelated Pathogens

Haiyan Liu,1,{dagger} Samita Andreansky,1 Gabriela Diaz,1 Stephen J. Turner,1 Dominik Wodarz,2,{ddagger} and Peter C. Doherty1*

Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105,1 Program in Theoretical Biology, Institute for Advanced Study, Princeton, New Jersey 085402

Received 11 October 2002/ Accepted 22 April 2003

The consequences for the long-term maintenance of virus-specific CD8+-T-cell memory have been analyzed experimentally for sequential respiratory infections with readily eliminated (influenza virus) and persistent (gammaherpesvirus 68 [{gamma}HV68]) pathogens. Sampling a broad range of tissue sites established that the numbers of CD8+ T cells specific for the prominent influenza virus DbNP366 epitope were reduced by about half in mice that had been challenged 100 days previously with {gamma}HV68, though the prior presence of a large CD8+ DbNP366+ population caused no selective defect in the {gamma}HV68-specific CD8+ Kbp79+ response. Conversely, mice that had been primed and boosted to generate substantial {gamma}HV68-specific CD8+ Dbp56+ populations did not show any decrease in prevalence for this set of CD8+ memory cytotoxic T lymphocytes (CTL) at 200 days after respiratory exposure to an influenza A virus. However, in both experiments, the total magnitude of the CD8+-T-cell pool was significantly diminished in those that had been infected with {gamma}HV68 and the influenza A virus. The broader implications of these findings, especially under conditions of repeated exposure to unrelated pathogens, are explored with a mathematical model which emphasizes that the immune effector and memory "phenome" is a function of the overall infection experience of the individual.

* 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: University of Nevada School of Medicine, Reno, NV 89557.

{ddagger} Present address: Fred Hutchinson Cancer Research Center, Seattle, WA 98109.

Journal of Virology, July 2003, p. 7756-7763, Vol. 77, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.14.7756-7763.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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