title: BST2/Tetherin is constitutively expressed on human thymocytes with the phenotype and function of Treg cells.
abstract: In contrast to peripheral plasmacytoid DCs (pDCs), thymic pDCs constitutively express low levels of IFN-α. This leads to induction of interferon secondary genes (ISGs) in medullary thymocytes, raising the question whether IFN-α may play a role in T-cell development. When characterizing further differences between peripheral and thymic pDCs, we found that thymic pDCs have a phenotype consistent with an "activated signature" including expression of TNF-α and bone marrow stromal cell antigen 2 (BST2), but no expression of ILT7. Given that BST2 is induced by IFN-α, and IFN-α secretion is controlled by interaction between ILT7 and BST2, this regulatory pathway is apparently lost in thymic pDCs. Further, we also show that BST2 is constitutively expressed on a subset of medullary thymocytes at the mRNA and protein level reflecting a history of IFN-α transduced signals. The majority of BST2(+) thymocytes express CCR5 rendering them prevalent targets for R5-tropic HIV infection. Moreover, BST2(+) thymocytes express Foxp3 and CD25, consistent with the phenotype of natural Treg cells, and exert suppressive activity as they impair the proliferation of autologous CD3(+) thymocytes. Collectively, our results suggest that low levels of IFN-α secreted by thymic pDCs play an important role in the development of natural Treg cells.
authors.affiliation: Departments of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, USA; UCLA AIDS Institute, UCLA, Los Angeles, CA, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Epeldegui
authors.forename: Bianca
authors.initials: B
authors.lastname: Blom
authors.forename: Christel H
authors.initials: CH
authors.lastname: Uittenbogaart
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism; D008297:Male; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D016898:Interferon-alpha; D019713:Receptors, CCR5; D011971:Receptors, Immunologic; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C584933:CCR5 protein, human; C488262:LILRA4 protein, human
keywords: ISG; Interferon-α; Plasmacytoid dendritic cells; Regulatory T-cells; Thymus