Memory CD8+ T cells are gatekeepers of the lymph node draining the site of viral infection
- *Program of Viral Pathogenesis and
- †Department of Pathology, Division of Basic Sciences, Fox Chase Cancer Center, Philadelphia, PA 19111
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Edited by Malcolm A. Martin, National Institutes of Health, Bethesda, MD, and approved May 14, 2007 (received for review February 27, 2007)
Abstract
It is uncertain how immunity protects against systemic viral diseases. Here, we demonstrate that in the absence of persistent virus, not only antibodies but also recall responses by long-lived memory CD8+ T cells prevent mousepox, a disease caused by ectromelia virus, a close relative of the virus of human smallpox. Moreover, we show that to protect, recall CD8+ T cells directly kill targets in the lymph node draining the primary site of infection thus curbing systemic viral spread. Therefore, our work provides the basis for a model where lymph nodes are not just organs where lymphocytes become activated and proliferate but also the sites where a major fight against virus spread takes place.
Footnotes
- ‡To whom correspondence should be addressed at: Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111. E-mail: luis.sigal{at}fccc.edu
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Author contributions: R.-H.X. and M.F. contributed equally to this work; R.-H.X., M.F., and L.J.S. designed research; R.-H.X. and M.F. performed research; R.-H.X., M.F., A.K.-S., and L.J.S. analyzed data; and L.J.S. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
- Abbreviations:
- D-LN,
- draining lymph node;
- ECTV,
- ectromelia virus;
- GzB,
- granzyme B;
- ND-LN,
- nondraining lymph node;
- OPV,
- orthopoxvirus(es);
- p.i.,
- postinfection;
- VACV,
- vaccinia virus.
- © 2007 by The National Academy of Sciences of the USA
