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Publication : IL-15-independent proliferative renewal of memory CD8+ T cells in latent gammaherpesvirus infection.

First Author  Obar JJ Year  2004
Journal  J Immunol Volume  173
Issue  4 Pages  2705-14
PubMed ID  15294989 Mgi Jnum  J:92657
Mgi Id  MGI:3054271 Doi  10.4049/jimmunol.173.4.2705
Citation  Obar JJ, et al. (2004) IL-15-independent proliferative renewal of memory CD8+ T cells in latent gammaherpesvirus infection. J Immunol 173(4):2705-14
abstractText  IL-15 is known to be critical in the homeostasis of Ag-specific memory CD8(+) T cells following acute viral infection. However, little is known about the homeostatic requirements of memory CD8(+) T cells during a latent viral infection. We have used the murine gammaherpesvirus-68 (MHV-68) model system to investigate whether IL-15 is necessary for the maintenance of memory CD8(+) T cells during a latent viral infection. IL-15 is not essential either for the initial control of MHV-68 infection or for the maintenance of MHV-68-specific memory CD8(+) T cells. Even at 140 days postinfection, the proportion of CD8(+) T cells recognizing the MHV-68 epitopes were the same as in control mice. The maintenance of these memory CD8(+) T cells was attributable to their ability to turn over in vivo, probably in response to the presence of low levels of Ag. IL-15(-/-) mice had a significantly higher turnover rate within the virus-specific memory CD8(+) T cell population, which was the result of increased levels of viral gene expression rather than an increase in viral load. These cells did not accumulate in the spleens of the IL-15(-/-) mice due to an increased sensitivity to apoptosis as a result of decreased Bcl-2 levels. Intriguingly, memory CD8(+) T cells from latently infected mice failed to undergo homeostatic proliferation in a naive secondary host. These data highlight fundamental differences between memory CD8(+) T cells engaged in active immune surveillance of latent viral infections vs memory CD8(+) T cells found after acute viral infections.
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