TY - JOUR
T1 - Adenosine deaminase regulates Treg expression in autologous T cell-dendritic cell cocultures from patients infected with HIV-1
AU - Naval-Macabuhay, Isaac
AU - Casanova, Víctor
AU - Navarro, Gemma
AU - García, Felipe
AU - León, Agathe
AU - Miralles, Laia
AU - Rovira, Cristina
AU - Martinez-Navio, José M.
AU - Gallart, Teresa
AU - Mallol, Josefa
AU - Gatell, José M.
AU - Lluís, Carme
AU - Franco, Rafael
AU - McCormick, Peter J.
AU - Climent, Núria
PY - 2016/2
Y1 - 2016/2
N2 - 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.
AB - 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.
KW - AIDS
KW - chemokine
KW - RANTES
KW - memory cells
KW - vaccine
U2 - 10.1189/jlb.3A1214-580RR
DO - 10.1189/jlb.3A1214-580RR
M3 - Article
VL - 99
SP - 349
EP - 359
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 2
ER -