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-Catenin Regulates Positive Selection of Thymocytes but Not Lineage Commitment¹

Lymphocyte Development Unit, Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224

Positive selection and lineage commitment to the cytolytic or helper lineage of T cells result in coordinated expression of MHC class I-restricted TCR and CD8 coreceptor or MHC class II-restricted TCR and CD4 molecule. Positive selection signals also regulate the survival and generation of requisite numbers of cytolytic or Th cells. -Catenin is the major transcriptional cofactor of T cell factor and plays a role in thymocyte development. In this study, using mice expressing stabilized -catenin and mice with T cell-specific deletion of -catenin, we show that -catenin regulates positive selection, but not lineage commitment of thymocytes. Furthermore, -catenin expression accelerates the timing of mature CD8 thymocyte generation such that CD4 and CD8 single-positive thymocytes mature with the same kinetics during development.

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¹ This work was supported by the Intramural Research Program of the National Institute on Aging at the National Institutes of Health.

² Address correspondence and reprint requests to Dr. Jyoti Misra Sen, Lymphocyte Development Unit, Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224. E-mail address: Jyoti-Sen{at}NIH.GOV

³ Abbreviations used in this paper: DP, double positive; CAT, -catenin transgene; DN, double negative; FTOC, fetal thymic organ culture; GSK-3, glycogen synthase kinase-3; KO, knockout; SP, single positive; Tg, transgenic.

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