title: Adenosine deaminase regulates Treg expression in autologous T cell-dendritic cell cocultures from patients infected with HIV-1.
abstract: Regulatory T cells have an important role in immune suppression during HIV-1 infection. As regulatory T cells produce the immunomodulatory molecule adenosine, our aim here was to assess the potential of adenosine removal to revert the suppression of anti-HIV responses exerted by regulatory T cells. The experimental setup consisted of ex vivo cocultures of T and dendritic cells, to which adenosine deaminase, an enzyme that hydrolyzes adenosine, was added. In cells from healthy individuals, adenosine hydrolysis decreased CD4(+)CD25(hi) regulatory T cells. Addition of 5'-N-ethylcarboxamidoadenosine, an adenosine receptor agonist, significantly decreased CD4(+)CD25(lo) cells, confirming a modulatory role of adenosine acting via adenosine receptors. In autologous cocultures of T cells with HIV-1-pulsed dendritic cells, addition of adenosine deaminase led to a significant decrease of HIV-1-induced CD4(+)CD25(hi) forkhead box p3(+) cells and to a significant enhancement of the HIV-1-specific CD4(+) responder T cells. An increase in the effector response was confirmed by the enhanced production of CD4(+) and CD8(+) CD25(-)CD45RO(+) memory cell generation and secretion of Th1 cytokines, including IFN-γ and IL-15 and chemokines MIP-1α/CCL3, MIP-1β/CCL4, and RANTES/CCL5. These ex vivo results show, in a physiologically relevant model, that adenosine deaminase is able to enhance HIV-1 effector responses markedly. The possibility to revert regulatory T cell-mediated inhibition of immune responses by use of adenosine deaminase, an enzyme that hydrolyzes adenosine, merits attention for restoring T lymphocyte function in HIV-1 infection.
authors: *Department of Biochemistry and Molecular Biology, Faculty of Biology, and Institute of Biomedicine of the University of Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer-AIDS Research Group and Catalonian Center for HIV Vaccines, Barcelona, Spain; Infectious Diseases and AIDS Unit and Service of Immunology, Hospital Clínic de Barcelona, Spain; and School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors: Isaac
authors: I
authors: Naval-Macabuhay
authors: *Department of Biochemistry and Molecular Biology, Faculty of Biology, and Institute of Biomedicine of the University of Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer-AIDS Research Group and Catalonian Center for HIV Vaccines, Barcelona, Spain; Infectious Diseases and AIDS Unit and Service of Immunology, Hospital Clínic de Barcelona, Spain; and School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors: Víctor
authors: V
authors: Casanova
authors: *Department of Biochemistry and Molecular Biology, Faculty of Biology, and Institute of Biomedicine of the University of Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer-AIDS Research Group and Catalonian Center for HIV Vaccines, Barcelona, Spain; Infectious Diseases and AIDS Unit and Service of Immunology, Hospital Clínic de Barcelona, Spain; and School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors: Gemma
authors: G
authors: Navarro
authors: *Department of Biochemistry and Molecular Biology, Faculty of Biology, and Institute of Biomedicine of the University of Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer-AIDS Research Group and Catalonian Center for HIV Vaccines, Barcelona, Spain; Infectious Diseases and AIDS Unit and Service of Immunology, Hospital Clínic de Barcelona, Spain; and School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors: Felipe
authors: F
authors: García
authors: *Department of Biochemistry and Molecular Biology, Faculty of Biology, and Institute of Biomedicine of the University of Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer-AIDS Research Group and Catalonian Center for HIV Vaccines, Barcelona, Spain; Infectious Diseases and AIDS Unit and Service of Immunology, Hospital Clínic de Barcelona, Spain; and School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors: Agathe
authors: A
authors: León
authors: *Department of Biochemistry and Molecular Biology, Faculty of Biology, and Institute of Biomedicine of the University of Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer-AIDS Research Group and Catalonian Center for HIV Vaccines, Barcelona, Spain; Infectious Diseases and AIDS Unit and Service of Immunology, Hospital Clínic de Barcelona, Spain; and School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors: Laia
authors: L
authors: Miralles
authors: *Department of Biochemistry and Molecular Biology, Faculty of Biology, and Institute of Biomedicine of the University of Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer-AIDS Research Group and Catalonian Center for HIV Vaccines, Barcelona, Spain; Infectious Diseases and AIDS Unit and Service of Immunology, Hospital Clínic de Barcelona, Spain; and School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors: Cristina
authors: C
authors: Rovira
authors: *Department of Biochemistry and Molecular Biology, Faculty of Biology, and Institute of Biomedicine of the University of Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer-AIDS Research Group and Catalonian Center for HIV Vaccines, Barcelona, Spain; Infectious Diseases and AIDS Unit and Service of Immunology, Hospital Clínic de Barcelona, Spain; and School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors: José M
authors: JM
authors: Martinez-Navio
authors: *Department of Biochemistry and Molecular Biology, Faculty of Biology, and Institute of Biomedicine of the University of Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer-AIDS Research Group and Catalonian Center for HIV Vaccines, Barcelona, Spain; Infectious Diseases and AIDS Unit and Service of Immunology, Hospital Clínic de Barcelona, Spain; and School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors: Teresa
authors: T
authors: Gallart
authors: *Department of Biochemistry and Molecular Biology, Faculty of Biology, and Institute of Biomedicine of the University of Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer-AIDS Research Group and Catalonian Center for HIV Vaccines, Barcelona, Spain; Infectious Diseases and AIDS Unit and Service of Immunology, Hospital Clínic de Barcelona, Spain; and School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors: Josefa
authors: J
authors: Mallol
authors: *Department of Biochemistry and Molecular Biology, Faculty of Biology, and Institute of Biomedicine of the University of Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer-AIDS Research Group and Catalonian Center for HIV Vaccines, Barcelona, Spain; Infectious Diseases and AIDS Unit and Service of Immunology, Hospital Clínic de Barcelona, Spain; and School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors: José M
authors: JM
authors: Gatell
authors: *Department of Biochemistry and Molecular Biology, Faculty of Biology, and Institute of Biomedicine of the University of Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer-AIDS Research Group and Catalonian Center for HIV Vaccines, Barcelona, Spain; Infectious Diseases and AIDS Unit and Service of Immunology, Hospital Clínic de Barcelona, Spain; and School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors: Carme
authors: C
authors: Lluís
authors: *Department of Biochemistry and Molecular Biology, Faculty of Biology, and Institute of Biomedicine of the University of Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer-AIDS Research Group and Catalonian Center for HIV Vaccines, Barcelona, Spain; Infectious Diseases and AIDS Unit and Service of Immunology, Hospital Clínic de Barcelona, Spain; and School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors: Rafael
authors: R
authors: Franco
authors: *Department of Biochemistry and Molecular Biology, Faculty of Biology, and Institute of Biomedicine of the University of Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer-AIDS Research Group and Catalonian Center for HIV Vaccines, Barcelona, Spain; Infectious Diseases and AIDS Unit and Service of Immunology, Hospital Clínic de Barcelona, Spain; and School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors: Peter J
authors: PJ
authors: McCormick
authors: *Department of Biochemistry and Molecular Biology, Faculty of Biology, and Institute of Biomedicine of the University of Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer-AIDS Research Group and Catalonian Center for HIV Vaccines, Barcelona, Spain; Infectious Diseases and AIDS Unit and Service of Immunology, Hospital Clínic de Barcelona, Spain; and School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom nucliment@yahoo.es ncliment@clinic.ub.es.
authors: Núria
authors: N
authors: Climent
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000243:Adenosine Deaminase / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018925:Chemokines / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects*; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018925:Chemokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D008222:Lymphokines; D058906:Purinergic P1 Receptor Agonists; D019830:Adenosine-5'-(N-ethylcarboxamide); C548482:ADA protein, human; D000243:Adenosine Deaminase; D000241:Adenosine
keywords: AIDS; RANTES; chemokine; memory cells; vaccine