title: Adenosine deaminase enhances the immunogenicity of human dendritic cells from healthy and HIV-infected individuals.
abstract: ADA is an enzyme implicated in purine metabolism, and is critical to ensure normal immune function. Its congenital deficit leads to severe combined immunodeficiency (SCID). ADA binding to adenosine receptors on dendritic cell surface enables T-cell costimulation through CD26 crosslinking, which enhances T-cell activation and proliferation. Despite a large body of work on the actions of the ecto-enzyme ADA on T-cell activation, questions arise on whether ADA can also modulate dendritic cell maturation. To this end we investigated the effects of ADA on human monocyte derived dendritic cell biology. Our results show that both the enzymatic and non-enzymatic activities of ADA are implicated in the enhancement of CD80, CD83, CD86, CD40 and CCR7 expression on immature dendritic cells from healthy and HIV-infected individuals. These ADA-mediated increases in CD83 and costimulatory molecule expression is concomitant to an enhanced IL-12, IL-6, TNF-α, CXCL8(IL-8), CCL3(MIP1-α), CCL4(MIP-1β) and CCL5(RANTES) cytokine/chemokine secretion both in healthy and HIV-infected individuals and to an altered apoptotic death in cells from HIV-infected individuals. Consistently, ADA-mediated actions on iDCs are able to enhance allogeneic CD4 and CD8-T-cell proliferation, globally yielding increased iDC immunogenicity. Taken together, these findings suggest that ADA would promote enhanced and correctly polarized T-cell responses in strategies targeting asymptomatic HIV-infected individuals.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Casanova
authors.forename: Isaac
authors.initials: I
authors.lastname: Naval-Macabuhay
authors.forename: Marta
authors.initials: M
authors.lastname: Massanella
authors.forename: Marta
authors.initials: M
authors.lastname: Rodríguez-García
authors.forename: Julià
authors.initials: J
authors.lastname: Blanco
authors.forename: José M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Felipe
authors.initials: F
authors.lastname: García
authors.forename: Teresa
authors.initials: T
authors.lastname: Gallart
authors.forename: Carme
authors.initials: C
authors.lastname: Lluis
authors.forename: Josefa
authors.initials: J
authors.lastname: Mallol
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
authors.forename: Núria
authors.initials: N
authors.lastname: Climent
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McCormick
mesh_terms: D000243:Adenosine Deaminase / Q000276:immunology / Q000378:metabolism; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007109:Immunity; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018047:Receptors, Purinergic P1 / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D018047:Receptors, Purinergic P1; D000243:Adenosine Deaminase