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

作者：Naval Macabuhay Isaac; Casanova Victor; Navarro Gemma; Garcia Felipe; Leon Agathe; Miralles Laia; Rovira Cristina; Martinez Navio Jose M; Gallart Teresa; Mallol Josefa; Gatell Jose M; Lluis Carme; Franco Rafael; McCormick Peter J; Climent Nuria^*

来源：Journal of Leukocyte Biology, 2016, 99(2): 349-359.

DOI：10.1189/jlb.3A1214-580RR

• AIDS
• chemokine
• RANTES
• memory cells
• vaccine

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-gamma and IL-15 and chemokines MIP-1 alpha/CCL3, MIP-1 beta/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.

• 出版日期2016-2