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Asymmetric T Lymphocyte Division in the Initiation of Adaptive Immune Responses
John T. Chang,1*Vikram R. Palanivel,1*Ichiko Kinjyo,1Felix Schambach,1Andrew M. Intlekofer,1Arnob Banerjee,1Sarah A. Longworth,1Kristine E. Vinup,1Paul Mrass,2Jane Oliaro,3Nigel Killeen,4Jordan S. Orange,5Sarah M. Russell,3,6Wolfgang Weninger,2Steven L. Reiner1
A hallmark of mammalian immunity is the heterogeneity of cellfate that exists among pathogen-experienced lymphocytes. Weshow that a dividing T lymphocyte initially responding to amicrobe exhibits unequal partitioning of proteins that mediatesignaling, cell fate specification, and asymmetric cell division.Asymmetric segregation of determinants appears to be coordinatedby prolonged interaction between the T cell and its antigen-presentingcell before division. Additionally, the first two daughter Tcells displayed phenotypic and functional indicators of beingdifferentially fated toward effector and memory lineages. Theseresults suggest a mechanism by which a single lymphocyte canapportion 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.
To whom correspondence should be addressed. E-mail: sreiner{at}mail.med.upenn.edu
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