Quantitative analysis of long-term virus-specific CD8 + -T-cell memory in mice challenged with unrelated pathogens

Haiyan Liu, Samita Andreansky, Gabriela Diaz, Stephen J. Turner, Dominik Wodarz, Peter C. Doherty

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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 [γHV681]) pathogens. Sampling a broad range of tissue sites established that the numbers of CD8 + T cells specific for the prominent influenza virus D b NP 366 epitope were reduced by about half in mice that had been challenged 100 days previously with γHV68, though the prior presence of a large CD8 + D b NP 366 + population caused no selective defect in the γHV68-specific CD8 + K b p79 + response. Conversely, mice that had been primed and boosted to generate substantial γHV68-specific CD8 + D b p56 + 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 γHV68 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.

Original languageEnglish
Pages (from-to)7756-7763
Number of pages8
JournalJournal of Virology
Issue number14
Publication statusPublished - 1 Jul 2003
Externally publishedYes

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