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
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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