Phenotypic and Functional Properties of Helios+ Regulatory T Cells

• Published in: PloS one Vol. 7; no. 3; p. e34547
• Main Authors: Zabransky, Daniel J., Nirschl, Christopher J., Durham, Nicholas M., Park, Ben V., Ceccato, Christina M., Bruno, Tullia C., Tam, Ada J., Getnet, Derese, Drake, Charles G.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.03.2012; Public Library of Science (PLoS)
• Subjects: Animals; Antigens, CD - genetics; Biology; CD103 antigen; Cell culture; Cell surface; Cloning; DNA-Binding Proteins - genetics; Flow cytometry; Foxp3 protein; Gene expression; Gene Expression Regulation, Neoplastic; Genotype & phenotype; Glucocorticoid-Induced TNFR-Related Protein - genetics; Ikaros protein; Immunology; Immunoregulation; In vivo methods and tests; Integrin alpha Chains - genetics; Lymphocytes; Lymphocytes T; Markers; Medicine; Mice; Mice, Inbred BALB C; Neoplasms - genetics; Oncology; Phenotype; Phosphatase; Protocol; Spleen - cytology; Splenocytes; Surface markers; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - metabolism; Thymus; Transcription factors; Transcription Factors - genetics; Up-Regulation; United States > US; Maryland; Baltimore Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0034547

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.