Histone Deacetylase 3 Is Required for Efficient T Cell Development.

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.

• Authors: Kristy R Stengel, Yue Zhao, Nicholas J Klus, Jonathan F Kaiser, Laura E Gordy, Sebastian Joyce, Scott W Hiebert, Alyssa R Summers
• Journal: Molecular and cellular biology (Mol Cell Biol) Vol. 35 Issue 22 Pg. 3854-65 (Nov 2015) ISSN: 1098-5549 [Electronic] United States
• PMID: 26324326 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Bcl2l1 protein, mouse
• CD4 Antigens
• CD8 Antigens
• Proto-Oncogene Proteins c-bcl-2
• Receptors, Antigen, T-Cell, alpha-beta
• bcl-X Protein
• Histone Deacetylases
• histone deacetylase 3

Topics

• Animals
• CD4 Antigens (analysis)
• CD4-Positive T-Lymphocytes (cytology, metabolism)
• CD8 Antigens (analysis)
• CD8-Positive T-Lymphocytes (cytology, metabolism)
• Cell Differentiation
• Gene Deletion
• Gene Expression Regulation, Developmental
• Histone Deacetylases (genetics)
• 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 (cytology, metabolism)
• bcl-X Protein (genetics)