Adenosine deaminase enhances the immunogenicity of human dendritic cells from healthy and HIV-infected individuals

Víctor Casanova, Isaac Naval-Macabuhay, Marta Massanella, Marta Rodríguez-García, Julià Blanco, José M Gatell, Felipe García, Teresa Gallart, Carme Lluis, Josefa Mallol, Rafael Franco, Núria Climent, Peter J McCormick

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.
Original languageEnglish
Article numbere51287
JournalPLoS One
Volume7
Issue number12
DOIs
Publication statusPublished - 11 Dec 2012

Keywords

  • Adenosine Deaminase
  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines
  • Dendritic Cells
  • Female
  • HIV Infections
  • HIV-1
  • Humans
  • Immunity
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Receptors, Purinergic P1

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