how does cross-reactive stimulation affect the longevity of cd8+ t cell memory可交叉反应的刺激是如何影响长寿的cd8 + t细胞记忆.pdfVIP

How Does Cross-Reactive Stimulation Affect the Longevity of CD8þ T Cell Memory? 1[¤ 2 3 1[* Vitaly V. Ganusov , Sergei S. Pilyugin , Rafi Ahmed , Rustom Antia 1 Department of Biology, Emory University, Atlanta, Georgia, United States of America, 2 Department of Mathematics, University of Florida, Gainesville Florida, United States of America, 3 Emory Vaccine Center, Emory University, Atlanta, Georgia, United States of America Immunological memory—the ability to ‘‘remember’’ previously encountered pathogens and respond faster upon re- exposure is a central feature of the immune response in vertebrates. The cross-reactive stimulation hypothesis for the maintenance of memory proposes that memory cells specific for a given pathogen are maintained by cross-reactive stimulation following infections with other (unrelated) pathogens. We use mathematical models to examine the cross- reactive stimulation hypothesis. We find that: (i) the direct boosting of cross-reactive lineages only provides a very small increase in the average longevity of immunological memory; (ii) the expansion of cross-reactive lineages can indirectly increase the longevity of memory by reducing the magnitude of expansion of new naive lineages which occupy space in the memory compartment and are responsible for the decline in memory; (iii) cross-reactive stimulation results in variation in the rates of decline of different lineages of memory cells and enrichment of memory cell population for cells that are cross-reactive for the pathogens to which the individual has been exposed. Citation: Ganusov VV, Pilyugin SS, Ahmed R, Antia R (2006) How does cross-reactive stimulation affect the longevity of CD8þ T cell memory? PLoS Comput Biol 2(6): e55. DOI: 10.1371/journal.pcbi.0020055 Intro