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Published Online March 1, 2007
Science DOI: 10.1126/science.1139393

Research Articles

Submitted on December 28, 2006
Accepted on February 8, 2007

Asymmetric T Lymphocyte Division in the Initiation of Adaptive Immune Responses

John T. Chang 1, Vikram R. Palanivel 1, Ichiko Kinjyo 1, Felix Schambach 1, Andrew M. Intlekofer 1, Arnob Banerjee 1, Sarah A. Longworth 1, Kristine E. Vinup 1, Paul Mrass 2, Jane Oliaro 3, Nigel Killeen 4, Jordan S. Orange 5, Sarah M. Russell 6, Wolfgang Weninger 2, Steven L. Reiner 1*

1 Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
2 Immunology Program, The Wistar Institute, Philadelphia, PA 19104, USA.
3 Immune Signalling Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria 2002, Australia.
4 Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA.
5 Department of Pediatrics, University of Pennsylvania, Philadelphia, PA 19104, USA.
6 Immune Signalling Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria 2002, Australia; Center for MicroPhotonics, Faculty of Engineering and Industrial Sciences, Swinburne University of Technology, Victoria 3122, Australia.

* To whom correspondence should be addressed.
Steven L. Reiner , E-mail: sreiner{at}mail.med.upenn.edu

A hallmark of mammalian immunity is the heterogeneity of cell fate that exists among pathogen-experienced lymphocytes. We now show that a dividing T lymphocyte initially responding to a microbe exhibits unequal partitioning of proteins that mediate signaling, cell fate specification, and asymmetric cell division. Asymmetric segregation of determinants appears to be coordinated by prolonged interaction between the T cell and its antigen-presenting cell prior to division. Additionally, the first two daughter T cells displayed phenotypic and functional indicators of being differentially fated toward effector and memory lineages. These results suggest a mechanism in which a single lymphocyte can apportion diverse cell fates necessary for adaptive immunity.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)