Immunosuppressive Treg cells acquire the phenotype of effector-T cells in chronic lymphocytic leukemia patients
Autor: | Serena De Matteis, Giovanni Martinelli, Giulia Abbati, Tania Rossi, Roberta Napolitano, Gerardo Musuraca, Daniele Calistri, Chiara Molinari, Pier Paolo Fattori, Andrea Ghelli Luserna di Rorà, Massimiliano Bonafè, Alessandro Lucchesi, Martina Ghetti, Antonio Cuneo, Gian Matteo Rigolin |
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Přispěvatelé: | De Matteis, Serena, Molinari, Chiara, Abbati, Giulia, Rossi, Tania, Napolitano, Roberta, Ghetti, Martina, Di Rorà, Andrea Ghelli Luserna, Musuraca, Gerardo, Lucchesi, Alessandro, Rigolin, Gian Matteo, Cuneo, Antonio, Calistri, Daniele, Fattori, Pier Paolo, Bonafè, Massimiliano, Martinelli, Giovanni |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Genetics and Molecular Biology (all)
Male Chronic lymphocytic leukemia lcsh:Medicine Adaptive Immunity Biochemistry Interleukin-23 T-Lymphocytes Regulatory 0302 clinical medicine Candida albicans Aged 80 and over medicine.diagnostic_test Gene Expression Regulation Leukemic CLL Effector-like Tregs Plasticity Tregs Biochemistry Genetics and Molecular Biology (all) General Medicine Middle Aged Acquired immune system Phenotype Treg medicine.anatomical_structure 030220 oncology & carcinogenesis Effector-like Treg Cytokines Female Immunosuppressive Agents T cell chemical and pharmacologic phenomena Peripheral blood mononuclear cell General Biochemistry Genetics and Molecular Biology NO Flow cytometry 03 medical and health sciences Interferon-gamma Immune system medicine Humans Aged Innate immune system business.industry Research Gene Expression Profiling lcsh:R medicine.disease Leukemia Lymphocytic Chronic B-Cell Immunity Innate Lymphocyte Subsets Immunology business 030215 immunology |
Zdroj: | Journal of Translational Medicine Journal of Translational Medicine, Vol 16, Iss 1, Pp 1-9 (2018) |
ISSN: | 1479-5876 |
Popis: | Background In chronic lymphocytic leukemia (CLL) disease onset and progression are influenced by the behavior of specific CD4+ T cell subsets, such as T regulatory cells (Tregs). Here, we focused on the phenotypic and functional characterization of Tregs in CLL patients to improve our understanding of the putative mechanism by which these cells combine immunosuppressive and effector-like properties. Methods Peripheral blood mononuclear cells were isolated from newly diagnosed CLL patients (n = 25) and healthy volunteers (n = 25). The phenotypic and functional characterization of Tregs and their subsets was assessed by flow cytometry. In vitro analysis of TH1, TH2, TH17 and Tregs cytokines was evaluated by IFN-γ, IL-4, IL-17A and IL-10 secretion assays. The transcriptional profiling of 84 genes panel was evaluated by RT2 Profiler PCR Array. Statistical analysis was carried out using exact non parametric Mann–Whitney U test. Results In all CLL samples, we found a significant increase in the frequency of IL-10-secreting Tregs and Tregs subsets, a significant rise of TH2 IL-4+ and TH17 IL-17A+ cells, and a higher percentage of IFN-γ/IL-10 and IL-4/IL-10 double-releasing CD4+ T cells. In addition, we also observed the up-regulation of innate immunity genes and the down-regulation of adaptive immunity ones. Conclusions Our data show that Tregs switch towards an effector-like phenotype in CLL patients. This multifaceted behavior is accompanied by an altered cytokine profiling and transcriptional program of immune genes, leading to a dysfunction in immune response in the peripheral blood environment of CLL patients. Electronic supplementary material The online version of this article (10.1186/s12967-018-1545-0) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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