title: Allergy-related changes in levels of CD8+CD25+FoxP3(bright) Treg cells and FoxP3 mRNA expression in peripheral blood: the role of IL-10 or TGF-beta.
abstract: There is an increasing body of evidence that alterations of regulatory T (Treg) cell numbers and functions lead to immune disorders. Accordingly, understanding the regulatory mechanisms that maintain peripheral regulatory T (Treg) cell homeostasis is key to the development of effective targeted biologic therapies. We previously demonstrated the effects of IL-10 or TGF-beta on distinct CD8+CD28- T cell subsets in vitro. Allergy-related changes of CD8+CD25+FoxP3(bright)Treg cells and FoxP3 mRNA expression in peripheral blood were assessed by means of multicolor flow cytometry and real-time polymerase chain reaction (RT-PCR). Co-stimulation of CD8+CD25+ T cells with anti-CD3/CD28 in the presence of either IL-10 or TGF-beta increased the frequency of CD8+CD25+FoxP3(bright)Treg cells in patients with asthma and controls. Likewise, CD8+CD25+ T cell activation with anti-CD3/CD28 and TGF-beta increased FoxP3mRNA expression in all groups. Anti-CD3/CD28 and IL-10 appeared to regulate FoxP3 mRNA expression in a phenotype-dependent manner. Specifically, co-stimulation by anti-CD3/CD28 and IL-10 markedly increased FoxP3 mRNA expression in the severe asthma group whereas it had opposite effects on this value in other groups. Taken altogether, these data suggest that IL-10 and TGF-beta may modulate FoxP3 expressions at the protein and mRNA levels in respect to their need for peripheral tolerance.
authors.affiliation: Department of Laboratory Diagnostics, Medical University of Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Eusebio
authors.affiliation: Department of Internal Medicine, Medical University of Lodz, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Kuna
authors.affiliation: Department of Laboratory Diagnostics, Medical University of Lodz, Poland.
authors.forename: L
authors.initials: L
authors.lastname: Kraszula
authors.affiliation: Department of Internal Medicine, Medical University of Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Kupczyk
authors.affiliation: Department of Laboratory Diagnostics, Medical University of Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Pietruczuk
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D006967:Hypersensitivity / Q000097:blood* / Q000276:immunology / Q000473:pathology; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10