title: Unconventional, adenosine-producing suppressor T cells induced by dendritic cells exposed to BPZE1 pertussis vaccine.
abstract: BPZE1 is a live attenuated pertussis vaccine that successfully completed a phase 1 safety trial. This article describes the induction of unconventional suppressor T cells-producing ADO by MDDCs exposed to BPZE1 (BPZE1-DC) through distinct ectoenzymatic pathways that limit the damaging effect of inflammation. BPZE1-DC induces CD4(+) and CD8(+) T lymphocytes to express 2 sets of ectoenzymes generating ADO: 1 set is part of the conventional CD39/CD73 pathway, which uses ATP as substrate, whereas the other is part of the CD38/CD203a/CD73 pathway and metabolizes NAD(+). The contribution of the ADO-generating ectoenzymes in the regulatory response was shown by: 1) selective inhibition of the enzymatic activities of CD39, CD73, and CD38; 2) the ability of suppressor T cells to convert exogenously added ATP and NAD(+) to ADO; and 3) a positive correlation between ectoenzyme expression, ADO levels, and suppression abilities. Thus, T lymphocytes activated by BPZE1-DC shift to a suppressor stage, through the expression of ectoenzyme networks, and are able to convert extracellular nucleotides into ADO, which may explain the potent anti-inflammatory properties of BPZE1 observed in several murine models.
authors.affiliation: *Anti-Infectious Immunity Unit, Department of Infectious Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy; INSERM U1019, Lille, France; CNRS UMR8204, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity, Lille, France; University of Lille Nord de France, Lille, France; Laboratory of Immunogenetics, Department of Medical Sciences and CERMS, University of Torino, Torino, Italy; **Transplantation Immunology Service, Città della Salute e della Scienza Hospital, Torino, Italy giorgio.fedele@iss.it.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Fedele
authors.affiliation: *Anti-Infectious Immunity Unit, Department of Infectious Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy; INSERM U1019, Lille, France; CNRS UMR8204, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity, Lille, France; University of Lille Nord de France, Lille, France; Laboratory of Immunogenetics, Department of Medical Sciences and CERMS, University of Torino, Torino, Italy; **Transplantation Immunology Service, Città della Salute e della Scienza Hospital, Torino, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Sanseverino
authors.affiliation: *Anti-Infectious Immunity Unit, Department of Infectious Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy; INSERM U1019, Lille, France; CNRS UMR8204, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity, Lille, France; University of Lille Nord de France, Lille, France; Laboratory of Immunogenetics, Department of Medical Sciences and CERMS, University of Torino, Torino, Italy; **Transplantation Immunology Service, Città della Salute e della Scienza Hospital, Torino, Italy.
authors.forename: Krizia
authors.initials: K
authors.lastname: D'Agostino
authors.affiliation: *Anti-Infectious Immunity Unit, Department of Infectious Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy; INSERM U1019, Lille, France; CNRS UMR8204, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity, Lille, France; University of Lille Nord de France, Lille, France; Laboratory of Immunogenetics, Department of Medical Sciences and CERMS, University of Torino, Torino, Italy; **Transplantation Immunology Service, Città della Salute e della Scienza Hospital, Torino, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Schiavoni
authors.affiliation: *Anti-Infectious Immunity Unit, Department of Infectious Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy; INSERM U1019, Lille, France; CNRS UMR8204, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity, Lille, France; University of Lille Nord de France, Lille, France; Laboratory of Immunogenetics, Department of Medical Sciences and CERMS, University of Torino, Torino, Italy; **Transplantation Immunology Service, Città della Salute e della Scienza Hospital, Torino, Italy.
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
authors.affiliation: *Anti-Infectious Immunity Unit, Department of Infectious Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy; INSERM U1019, Lille, France; CNRS UMR8204, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity, Lille, France; University of Lille Nord de France, Lille, France; Laboratory of Immunogenetics, Department of Medical Sciences and CERMS, University of Torino, Torino, Italy; **Transplantation Immunology Service, Città della Salute e della Scienza Hospital, Torino, Italy.
authors.forename: Alberto L
authors.initials: AL
authors.lastname: Horenstein
authors.affiliation: *Anti-Infectious Immunity Unit, Department of Infectious Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy; INSERM U1019, Lille, France; CNRS UMR8204, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity, Lille, France; University of Lille Nord de France, Lille, France; Laboratory of Immunogenetics, Department of Medical Sciences and CERMS, University of Torino, Torino, Italy; **Transplantation Immunology Service, Città della Salute e della Scienza Hospital, Torino, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Malavasi
authors.affiliation: *Anti-Infectious Immunity Unit, Department of Infectious Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy; INSERM U1019, Lille, France; CNRS UMR8204, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity, Lille, France; University of Lille Nord de France, Lille, France; Laboratory of Immunogenetics, Department of Medical Sciences and CERMS, University of Torino, Torino, Italy; **Transplantation Immunology Service, Città della Salute e della Scienza Hospital, Torino, Italy.
authors.forename: Clara M
authors.initials: CM
authors.lastname: Ausiello
mesh_terms: D000241:Adenosine / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D010567:Pertussis Vaccine / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D010567:Pertussis Vaccine; D014613:Vaccines, Attenuated; D000241:Adenosine
keywords: ectoenzymes; nucleotides; regulatory T cells