title: Recent thymic emigrants and mature naive T cells exhibit differential DNA methylation at key cytokine loci.
abstract: Recent thymic emigrants (RTEs) are the youngest T cells in the lymphoid periphery and exhibit phenotypic and functional characteristics distinct from those of their more mature counterparts in the naive peripheral T cell pool. We show in this study that the Il2 and Il4 promoter regions of naive CD4(+) RTEs are characterized by site-specific hypermethylation compared with those of both mature naive (MN) T cells and the thymocyte precursors of RTEs. Thus, RTEs do not merely occupy a midpoint between the thymus and the mature T cell pool, but represent a distinct transitional T cell population. Furthermore, RTEs and MN T cells exhibit distinct CpG DNA methylation patterns both before and after activation. Compared with MN T cells, RTEs express higher levels of several enzymes that modify DNA methylation, and inhibiting methylation during culture allows RTEs to reach MN T cell levels of cytokine production. Collectively, these data suggest that the functional differences that distinguish RTEs from MN T cells are influenced by epigenetic mechanisms and provide clues to a mechanistic basis for postthymic maturation.
authors.affiliation: Department of Immunology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Berkley
authors.forename: Deborah W
authors.initials: DW
authors.lastname: Hendricks
authors.forename: Kalynn B
authors.initials: KB
authors.lastname: Simmons
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Fink
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D002469:Cell Separation; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D019175:DNA Methylation / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D060168:Thymocytes / Q000166:cytology* / Q000276:immunology
chemical_list: D016207:Cytokines; D007376:Interleukin-2; D015847:Interleukin-4