Adenosine deaminase regulates Treg expression in autologous T cell-dendritic cell cocultures from patients infected with HIV-1

Isaac Naval-Macabuhay, Víctor Casanova, Gemma Navarro, Felipe García, Agathe León, Laia Miralles, Cristina Rovira, José M. Martinez-Navio, Teresa Gallart, Josefa Mallol, José M. Gatell, Carme Lluís, Rafael Franco, Peter J. McCormick, Núria Climent (Lead Author)

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13 Citations (Scopus)

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+CD25hi regulatory T cells. Addition of 5'-N-ethylcarboxamidoadenosine, an adenosine receptor agonist, significantly decreased CD4+CD25lo 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+CD25hi 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.
Original languageEnglish
Pages (from-to)349-359
Number of pages11
JournalJournal of Leukocyte Biology
Volume99
Issue number2
Early online date26 Aug 2015
DOIs
Publication statusPublished - Feb 2016

Keywords

  • AIDS
  • chemokine
  • RANTES
  • memory cells
  • vaccine

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