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Originally published in Science Express on 2 March 2006
Science 7 April 2006:
Vol. 312. no. 5770, pp. 114 - 116
DOI: 10.1126/science.1124228
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Reports

Naïve and Memory CD4+ T Cell Survival Controlled by Clonal Abundance

Jason Hataye,1* James J. Moon,1 Alexander Khoruts,2 Cavan Reilly,3 Marc K. Jenkins1

Immunity to a plethora of microbes depends on a diverse repertoire of naïve lymphocytes and the production of long-lived memory cells. We present evidence here that low clonal abundance in a polyclonal repertoire favors the survival and activation of naïve CD4+ T cells as well as the survival of their memory cell progeny. The inverse relation between clonal frequency and survival suggests that intraclonal competition could help maintain an optimally diverse repertoire of T cells and an optimal environment for the generation of long-lived memory cells.

1 Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
2 Department of Medicine, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
3 Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN 55455, USA.

* To whom correspondence should be addressed. E-mail: hata0006{at}umn.edu

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   Abstract »    Full Text »    PDF »
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