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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2797-2805.
Prepublished online as a Blood First Edition Paper on December 15, 2005; DOI 10.1182/blood-2005-08-3103.
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Submitted August 3, 2005
Accepted November 13, 2005
T-bet concomitantly controls migration, survival and effector functions during the development of V 14i NKT cells
Jennifer L Matsuda, Qianjun Zhang, Rachel Ndonye, Stewart K Richardson, Amy R Howell, and Laurent Gapin*
Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Science Center, Denver, CO, USA
Department of Chemistry, University of Connecticut, Storrs, CT, USA
* Corresponding author; email: gapinl{at}njc.org.
V 14i NKT cell function has been implicated in a number of disease conditions. The molecular events that drive V 14i NKT cell development remain elusive. We recently showed that T-bet is required for the terminal maturation of these cells. Here we identify some of the genetic targets of T-bet during V 14i NKT cell lineage development. Microarray gene expression analyses on developing V 14i NKT cells were performed and provide a molecular framework to study these maturation events. In vitro ectopic expression of T-bet in immature V 14i NKT cells, which do not yet express T-bet, was sufficient to promote V 14i NKT cell maturation, driving the expression of multiple genes, including those that participate in migration, survival and effector functions. By regulating the expression of Th1-associated cytokines, chemokines, chemokine receptors and molecules involved in cytolysis, T-bet defines the unique lineage attributes of mature V 14i NKT cells and acts to link these attributes to a developmental process.

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