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

Naval-Macabuhay, Isaac, Casanova, Víctor, Navarro, Gemma, García, Felipe, León, Agathe, Miralles, Laia, Rovira, Cristina, Martinez-Navio, José M., Gallart, Teresa, Mallol, Josefa, Gatell, José M., Lluís, Carme, Franco, Rafael, McCormick, Peter J. and Climent, Núria (2016) Adenosine deaminase regulates Treg expression in autologous T cell-dendritic cell cocultures from patients infected with HIV-1. Journal of Leukocyte Biology, 99 (2). pp. 349-359. ISSN 0741-5400

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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.

Item Type:	Article
Uncontrolled Keywords:	aids,chemokine,rantes,memory cells,vaccine,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Pharmacy
Depositing User:	Pure Connector
Date Deposited:	05 Feb 2016 08:12
Last Modified:	21 Oct 2022 01:12
URI:	https://ueaeprints.uea.ac.uk/id/eprint/56950
DOI:	10.1189/jlb.3A1214-580RR

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