Distinct MBI-1 and EZH2 expression patterns in thymocytes and mature T cells suggest a role for Polycomb genes in human T cell differentiation

Autor: Karien M. Hamer, Folkert J. van Kemenade, Chris J.L.M. Meijer, Elly Fieret, Arie P. Otte, Frank M. Raaphorst, Tjasso Blokzijl, David P. E. Satijn
Přispěvatelé: Epigenetic Regulation of Gene Expression (inactive) (SILS, FNWI)
Rok vydání: 2001
Předmět:
Zdroj: The journal of immunology, 166, 5925-5934. American Association of Immunologists
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.166.10.5925
Popis: BMI-1 and EZH2 Polycomb-group (PcG) proteins belong to two distinct protein complexes involved in the regulation of hematopoiesis. Using unique PcG-specific antisera and triple immunofluorescence, we found that mature resting peripheral T cells expressed BMI-1, whereas dividing blasts were EZH2+. By contrast, subcapsular immature double-negative (DN) (CD4−/CD8−) T cells in the thymus coexpressed BMI-1 and EZH2 or were BMI-1 single positive. Their descendants, double-positive (DP; CD4+/CD8+) cortical thymocytes, expressed EZH2 without BMI-1. Most EZH2+ DN and DP thymocytes were dividing, while DN BMI-1+/EZH2− thymocytes were resting and proliferation was occasionally noted in DN BMI-1+/EZH2+ cells. Maturation of DP cortical thymocytes to single-positive (CD4+/CD8− or CD8+/CD4−) medullar thymocytes correlated with decreased detectability of EZH2 and continued relative absence of BMI-1. Our data show that BMI-1 and EZH2 expression in mature peripheral T cells is mutually exclusive and linked to proliferation status, and that this pattern is not yet established in thymocytes of the cortex and medulla. T cell stage-specific PcG expression profiles suggest that PcG genes contribute to regulation of T cell differentiation. They probably reflect stabilization of cell type-specific gene expression and irreversibility of lineage choice. The difference in PcG expression between medullar thymocytes and mature interfollicular T cells indicates that additional maturation processes occur after thymocyte transportation from the thymus.
Databáze: OpenAIRE
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