Immunosuppressive Treg cells acquire the phenotype of effector-T cells in chronic lymphocytic leukemia patients

Serena De Matteis, Chiara Molinari, Giulia Abbati, Tania Rossi, Roberta Napolitano, Martina Ghetti, Andrea Ghelli Luserna Di Rorà, Gerardo Musuraca, Alessandro Lucchesi, Gian Matteo Rigolin, Antonio Cuneo, Daniele Calistri, Pier Paolo Fattori, Massimiliano Bonafè, Giovanni Martinelli

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number172
JournalJournal of Translational Medicine
Volume16
Issue number1
DOIs
Publication statusPublished - Jun 20 2018

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T-Cell Prolymphocytic Leukemia
T-cells
Regulatory T-Lymphocytes
B-Cell Chronic Lymphocytic Leukemia
Immunosuppressive Agents
Interleukin-10
Interleukin-4
Phenotype
Interleukin-17
Genes
Blood
T-Lymphocyte Subsets
Cytokines
Flow cytometry
Assays
Statistical methods
Switches
Adaptive Immunity
Nonparametric Statistics
Innate Immunity

Keywords

  • CLL
  • Effector-like Tregs
  • Plasticity
  • Tregs

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Immunosuppressive Treg cells acquire the phenotype of effector-T cells in chronic lymphocytic leukemia patients. / 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.

In: Journal of Translational Medicine, Vol. 16, No. 1, 172, 20.06.2018.

Research output: Contribution to journalArticle

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. / Immunosuppressive Treg cells acquire the phenotype of effector-T cells in chronic lymphocytic leukemia patients. In: Journal of Translational Medicine. 2018 ; Vol. 16, No. 1.
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abstract = "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.",
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AU - De Matteis, Serena

AU - Molinari, Chiara

AU - Abbati, Giulia

AU - Rossi, Tania

AU - Napolitano, Roberta

AU - Ghetti, Martina

AU - Di Rorà, Andrea Ghelli Luserna

AU - Musuraca, Gerardo

AU - Lucchesi, Alessandro

AU - Rigolin, Gian Matteo

AU - Cuneo, Antonio

AU - Calistri, Daniele

AU - Fattori, Pier Paolo

AU - Bonafè, Massimiliano

AU - Martinelli, Giovanni

PY - 2018/6/20

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N2 - 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.

AB - 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.

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