title: Phenotypic and functional properties of Helios+ regulatory T cells.
abstract: Helios, an Ikaros family transcription factor, is preferentially expressed at the mRNA and protein level in regulatory T cells. Helios expression previously appeared to be restricted to thymic-derived Treg. Consistent with recent data, we show here that Helios expression is inducible in vitro under certain conditions. To understand phenotypic and functional differences between Helios(+) and Helios(-) Treg, we profiled cell-surface markers of FoxP3(+) Treg using unmanipulated splenocytes. We found that CD103 and GITR are expressed at high levels on a subset of Helios(+) Treg and that a Helios(+) Treg population could be significantly enriched by FACS sorting using these two markers. Quantitative real-time PCR (qPCR) analysis revealed increased TGF-β message in Helios(+) Treg, consistent with the possibility that this population possesses enhanced regulatory potential. In tumor-bearing mice, we found that Helios(+) Treg were relatively over-represented in the tumor-mass, and BrdU studies showed that, in vivo, Helios(+) Treg proliferated more than Helios(-) Treg. We hypothesized that Helios-enriched Treg might exert increased suppressive effects. Using in vitro suppression assays, we show that Treg function correlates with the absolute number of Helios(+) cells in culture. Taken together, these data show that Helios(+) Treg represent a functional subset with associated CD103 and GITR expression.
authors.affiliation: Department of Oncology, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Zabransky
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Nirschl
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Durham
authors.forename: Ben V
authors.initials: BV
authors.lastname: Park
authors.forename: Christina M
authors.initials: CM
authors.lastname: Ceccato
authors.forename: Tullia C
authors.initials: TC
authors.lastname: Bruno
authors.forename: Ada J
authors.initials: AJ
authors.lastname: Tam
authors.forename: Derese
authors.initials: D
authors.lastname: Getnet
authors.forename: Charles G
authors.initials: CG
authors.lastname: Drake
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000235:genetics; D039001:Integrin alpha Chains / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000235:genetics; D010641:Phenotype; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D004268:DNA-Binding Proteins; D053450:Glucocorticoid-Induced TNFR-Related Protein; D039001:Integrin alpha Chains; C106544:Tnfrsf18 protein, mouse; D014157:Transcription Factors; C491746:Zfpn1a2 protein, mouse; C091367:alpha E integrins