Naval-Macabuhay I.,University of Barcelona |
Casanova V.,University of Barcelona |
Navarro G.,University of Barcelona |
Garcia F.,Institute Dinvestigacions Biomediques August Pi nyer Aids Research Group And Catalonian Center For Hiv Vaccines |
And 14 more authors.
Journal of Leukocyte Biology | Year: 2016
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+CD25hiregulatory 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. © Society for Leukocyte Biology.