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

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

Abstract

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 [γHV68]) 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

Topics: Pathogenesis and Immunity
Publisher: American Society for Microbiology
Year: 2003
DOI identifier: 10.1128/JVI.77.14.7756-7763.2003
OAI identifier: oai:pubmedcentral.nih.gov:161950
Provided by: PubMed Central
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