title: Advancements on phenotypic and functional characterization of non-antigen-specific CD8+CD28- regulatory T cells.
abstract: Among the different regulatory T lymphocyte (Treg) subpopulations, non-antigen-specific CD8+CD28- Treg (CD8+CD28- Treg) have been characterized for being involved in the pathogenesis of autoimmune diseases and cancer. A better phenotypic and functional characterization of this regulatory T-cell subset could help in identifying modulators of their activity with therapeutic finalities. The results of the present work show that Foxp3, a transcriptional marker of natural CD4+CD25+ Treg, is not expressed by CD8+CD28- Treg, thus indicating different origin and pathways of function for the latter with respect to the former regulatory cell type. Moreover, the results underline that the glucocorticoid induced TNF receptor is involved in generation processes but not in suppressor function of CD8+CD28- Treg. Phenotypic analyses demonstrate that, during their commitment from circulating nonregulatory CD8+CD28- T lymphocytes to Treg (an interleukin-10-dependent process), these cells downmodulate the IL7-receptor, thus differentiating them from long-lived, memory CD8+ T lymphocytes. Interestingly, CD8+CD28- Treg have been found to be resistant to the inhibitory effects of methylprednisolone, one of the most frequently administered corticosteroid drug used in therapy for immunosuppressive purposes.
authors.affiliation: Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Fenoglio
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrera
authors.forename: Marco
authors.initials: M
authors.lastname: Fravega
authors.forename: Piercesare
authors.initials: P
authors.lastname: Balestra
authors.forename: Florinda
authors.initials: F
authors.lastname: Battaglia
authors.forename: Michele
authors.initials: M
authors.lastname: Proietti
authors.forename: Cristina
authors.initials: C
authors.lastname: Andrei
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
authors.forename: La Cava
authors.initials: LC
authors.lastname: Antonio
authors.forename: Francesco
authors.initials: F
authors.lastname: Indiveri
authors.forename: Gilberto
authors.initials: G
authors.lastname: Filaci
mesh_terms: D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D008775:Methylprednisolone / Q000494:pharmacology; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D018106:CD28 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D005938:Glucocorticoids; C508609:IL10 protein, human; C109985:IL17RA protein, human; D053722:Receptors, Interleukin-17; D018124:Receptors, Tumor Necrosis Factor; D016753:Interleukin-10; D008775:Methylprednisolone