Quantitative analysis of long-term virus-specific CD8+-T-cell memory in mice challenged with unrelated pathogens.
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 [gammaHV68]) 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 gammaHV68, though the prior presence of a large CD8+ D(b)NP366+ population caused no selective defect in the gammaHV68-specific CD8+ K(b)p79+ response. Conversely, mice that had been primed and boosted to generate substantial gammaHV68-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 gammaHV68 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.
Liu
Haiyan
H
Department of Immunology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA.
Andreansky
Samita
S
Diaz
Gabriela
G
Turner
Stephen J
SJ
Wodarz
Dominik
D
Doherty
Peter C
PC
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D018142:Gammaherpesvirinae / Q000472:pathogenicity*; D006566:Herpesviridae Infections / Q000276:immunology / Q000821:virology; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D013997:Time Factors