Azodicarbonamide inhibits T-cell responses in vitro and in vivo

Azodicarbonamide was recently identified as a new anti-HIV agent that targe ts the zinc finger domains of the HIV-1 NCp7 nucleocapsid protein(1-3). Her e, we demonstrate that azodicarbonamide inhibits in a dose-dependent manner the responses of purified human CD4(+) T lymphocytes stimulated either by monoclonal antibodies against CD3 and CD28 or by allogeneic dendritic cells . These suppressive effects involve a direct action on the calcium mobiliza tion machinery, as azodicarbonamide strongly inhibited the calcium influx i nduced either by antibodies against CD3 and CD28 or the chemokine RANTES, a s well as by thapsigargin, an activator of depletion-activated calcium chan nels. In vivo, administration of azodicarbonamide into mice blunted their r esponse to polyclonal T-cell activation induced by the injection of monoclo nal antibody against CD3 and resulted in delayed rejection of skin allograf ts. In addition to its anti-HIV properties, azodicarbonamide is a new immun osuppressive agent that might have therapeutic applications in T cell-media ted inflammatory disorders.