An optimized CD8+ T-cell response controls productive and latent gammaherpesvirus infection

Douglas C. Braaten, Rebecca L. Sparks-Thissen, Scott Kreher, Samuel H. Speck, Herbert W. Virgin IV

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Strategies to prime CD8+ T cells against Murine gammaherpesvirus 68 (γHV68; MHV68) latency have, to date, resulted in only limited elects. While early forms of latency (<21 days) were significantly reduced, effects were not seen at later times, indicating loss of control by the primed CD8 + T cells. In the present study, we evaluated CD8+ T cells in an optimized system, consisting of OTI T-cell-receptor (TCR) transgenic mice, which generate clonal CD8+ T cells specific for K b-SIINFEKL of OVA, and a recombinant γHV68 that expresses OVA (γHV68.OVA). Our aim was to test whether this optimized system would result in more effective control not only of acute infection but also of later forms of latent infection than was seen with previous strategies. First, we show that OTI CD8+ T cells effectively controlled acute replication of γHV68.OVA in liver, lung, and spleen at 8 and 16 days after infection of OTI/RAG mice, which lack expression of B and CD4+ T cells. However, we found that, despite eliminating detectable acute replication, the OTI CD8+ T cells did not prevent the establishment of latency in the OTI/RAG mice. We next evaluated the effectiveness of OTI T cells in OTI/B6 animals, which express B cells - a major site of latency in wild-type mice - and CD4+ T cells. In OTI/B6 mice OTI CD8+ T cells not only reduced the frequency of cells that reactivate from latency and the frequency of cells bearing the viral genome at 16 days after infection (similar to what has been reported before) but also were effective at reducing latency at 42 days after infection. Together, these data show that CD8+ T cells are sufficient, in the absence of B cells and CD4+ T cells, for effective control of acute replication. The data also demonstrate for the first time that a strong CD8+ T-cell response can limit long-term latent infection.

Original languageEnglish
Pages (from-to)2573-2583
Number of pages11
JournalJournal of virology
Volume79
Issue number4
DOIs
StatePublished - Feb 2005

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