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Science 315 (5819): 1687-1691

Copyright © 2007 by the American Association for the Advancement of Science

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,3,6 Wolfgang Weninger,2 Steven L. Reiner1{dagger}

Abstract: A hallmark of mammalian immunity is the heterogeneity of cell fate that exists among pathogen-experienced lymphocytes. We 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 before 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 by which a single lymphocyte can apportion diverse cell fates necessary for adaptive immunity.

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 Center for MicroPhotonics, Faculty of Engineering and Industrial Sciences, Swinburne University of Technology, Victoria 3122, Australia.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: sreiner{at}mail.med.upenn.edu

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