1. Histone Deacetylase 3 Is Required for Efficient T Cell Development.
- Author
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Stengel KR, Zhao Y, Klus NJ, Kaiser JF, Gordy LE, Joyce S, Hiebert SW, and Summers AR
- Subjects
- Animals, CD4 Antigens analysis, CD4-Positive T-Lymphocytes cytology, CD4-Positive T-Lymphocytes metabolism, CD8 Antigens analysis, CD8-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes metabolism, Cell Differentiation, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Proto-Oncogene Proteins c-bcl-2 genetics, Receptors, Antigen, T-Cell, alpha-beta genetics, T-Lymphocytes metabolism, bcl-X Protein genetics, Gene Deletion, Gene Expression Regulation, Developmental, Histone Deacetylases genetics, T-Lymphocytes cytology
- Abstract
Hdac3 is a key target for Hdac inhibitors that are efficacious in cutaneous T cell lymphoma. Moreover, the regulation of chromatin structure is critical as thymocytes transition from an immature cell with open chromatin to a mature T cell with tightly condensed chromatin. To define the phenotypes controlled by Hdac3 during T cell development, we conditionally deleted Hdac3 using the Lck-Cre transgene. This strategy inactivated Hdac3 in the double-negative stages of thymocyte development and caused a significant impairment at the CD8 immature single-positive (ISP) stage and the CD4/CD8 double-positive stage, with few mature CD4(+) or CD8(+) single-positive cells being produced. When Hdac3(-/-) mice were crossed with Bcl-xL-, Bcl2-, or TCRβ-expressing transgenic mice, a modest level of complementation was found. However, when the null mice were crossed with mice expressing a fully rearranged T cell receptor αβ transgene, normal levels of CD4 single-positive cells were produced. Thus, Hdac3 is required for the efficient transit from double-negative stage 4 through positive selection., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
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