Azodicarbonamide inhibits T-cell responses in vitro and in vivo.
Azodicarbonamide was recently identified as a new anti-HIV agent that targets the zinc finger domains of the HIV-1 NCp7 nucleocapsid protein. Here, 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 mobilization machinery, as azodicarbonamide strongly inhibited the calcium influx induced either by antibodies against CD3 and CD28 or the chemokine RANTES, as well as by thapsigargin, an activator of depletion-activated calcium channels. In vivo, administration of azodicarbonamide into mice blunted their response to polyclonal T-cell activation induced by the injection of monoclonal antibody against CD3 and resulted in delayed rejection of skin allografts. In addition to its anti-HIV properties, azodicarbonamide is a new immunosuppressive agent that might have therapeutic applications in T cell-mediated inflammatory disorders.
Tassignon
J
J
Laboratory of Experimental Immunology, Université Libre de Bruxelles, Brussels, Belgium.
Ismaili
J
J
Le Moine
A
A
Van Laethem
F
F
Leo
O
O
Vandevelde
M
M
Goldman
M
M
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D001391:Azo Compounds / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation / Q000276:immunology
D019380:Anti-HIV Agents; D001391:Azo Compounds; C004525:azodicarbonamide; D002118:Calcium