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Naval-Macabuhay IAuthorGarcia FAuthorLeon AAuthorMiralles LAuthorRovira CAuthorMartinez-Navio JmAuthorGatell JmAuthorCliment NCorresponding Author

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

Publicated to:Journal Of Leukocyte Biology. 99 (2): 349-359 - 2016-02-01 99(2), DOI: 10.1189/jlb.3A1214-580RR

Authors: Naval-Macabuhay I., Casanova V., Navarro G., García F., León A., Miralles L., Rovira C., Martinez-Navio J., Gallart T., Mallol J., Gatell J., Llúis C., Franco R., McCormick P., Climent N.

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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(+)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-? and IL-15 and chemokines MIP-1?/CCL3, MIP-1?/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. © Society for Leukocyte Biology.

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