T Cell Costimulation by Derivatives of Benzoic Acid

A number of analogues of benzoic acid were evaluated in a T cell costimulation assay. One compound, the sodium salt of 2-chloro-5-nitrobenzoic acid (CNBA-Na) was chosen for further study and was found to be a potent costimulator of anti-CD3-induced proliferation of both H9 lymphoblastoid cells ( P<0.001) and human peripheral blood mononuclear cells ( P=0.001) in a dose-dependent manner. The costimulatory effect of CNBA-Na on CD3-triggered DNA synthesis did not enhance human immunodeficiency virus replication in infected cells. Studies with blocking monoclonal antibodies against B7-1 or B7-2 indicated that the immunopotentiatory effect of CNBA-Na required a macromolecular interaction between CD28 (a costimulatory receptor on T cells) and its counter receptor B7 expressed on antigen-presenting cells. The discovery that this low molecular weight compound causes T cell proliferation highlights a potentially novel therapeutic approach to immunodeficiency diseases.