Histone Deacetylase 3 Is Required for T Cell Maturation.

Hsu FC, Belmonte PJ, Constans MM, Chen MW, McWilliams DC, Hiebert SW, Shapiro VS
J Immunol. 2015 195 (4): 1578-90

PMID: 26163592 · PMCID: PMC4530026 · DOI:10.4049/jimmunol.1500435

Recent thymic emigrants are newly generated T cells that need to undergo postthymic maturation to gain functional competency and enter the long-lived naive T cell pool. The mechanism of T cell maturation remains incompletely understood. Previously, we demonstrated that the transcriptional repressor NKAP is required for T cell maturation. Because NKAP associates with histone deacetylase 3 (HDAC3), we examined whether HDAC3 is also required for T cell maturation. Although thymic populations are similar in CD4-cre HDAC3 conditional knockout mice compared with wild-type mice, the peripheral numbers of CD4(+) and CD8(+) T cells are dramatically decreased. In the periphery, the majority of HDAC3-deficient naive T cells are recent thymic emigrants, indicating a block in T cell maturation. CD55 upregulation during T cell maturation is substantially decreased in HDAC3-deficient T cells. Consistent with a block in functional maturation, HDAC3-deficient peripheral T cells have a defect in TNF licensing after TCR/CD28 stimulation. CD4-cre HDAC3 conditional knockout mice do not have a defect in intrathymic migration, thymic egress, T cell survival, or homeostasis. In the periphery, similar to immature NKAP-deficient peripheral T cells, HDAC3-deficient peripheral T cells were bound by IgM and complement proteins, leading to the elimination of these cells. In addition, HDAC3-deficient T cells display decreases in the sialic acid modifications on the cell surface that recruit natural IgM to initiate the classical complement pathway. Therefore, HDAC3 is required for T cell maturation.

Copyright © 2015 by The American Association of Immunologists, Inc.

MeSH Terms (17)

Animals Bone Marrow Cells Cell Differentiation Cell Movement Complement Activation Complement System Proteins Histone Deacetylases Homeostasis Interleukin-7 Lymphocyte Count Mice Mice, Knockout Mice, Transgenic T-Lymphocytes T-Lymphocyte Subsets Thymus Gland Tumor Necrosis Factors

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