Histone deacetylase 3 is required for T cell maturation

Fan Chi Hsu, Paul J. Belmonte, Megan M. Constans, Meibo W. Chen, Douglas C. McWilliams, Scott W. Hiebert, Virginia Smith Shapiro

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1578-1590
Number of pages13
JournalJournal of Immunology
Volume195
Issue number4
DOIs
StatePublished - Aug 15 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Hsu, F. C., Belmonte, P. J., Constans, M. M., Chen, M. W., McWilliams, D. C., Hiebert, S. W., & Shapiro, V. S. (2015). Histone deacetylase 3 is required for T cell maturation. Journal of Immunology, 195(4), 1578-1590. https://doi.org/10.4049/jimmunol.1500435