The immunosuppressive properties of a
benzamide derivative,
JM34, previously characterized as an anti-inflammatory compound are described. The immunosuppressive potential of
JM34 was evidenced by inhibition of PBMC proliferation in vitro with an IC50 of 20 microM. In contrast with classical immunosuppressive drugs,
JM34 affected neither
cytokine production nor IL-2R expression from activated T cell clones, and displayed only moderate inhibition of IL-2-induced or anti-CD3/anti-CD28-induced proliferation. We investigated its effects on dendritic cells (DC) in vitro. Addition of
JM34 during DC maturation inhibited the expression of some maturation markers: specifically, MHC molecule up-regulation was totally inhibited and CD83 expression was significantly reduced, while up-regulation of CD86, CD80 or CD40 was less affected. Moreover, JM34-treated DC showed impaired
IL-12 but not
IL-10 secretion, and a markedly reduced ability to present
antigens to naive T lymphocytes in vitro. We provide evidence that these JM34-induced alterations of DC were associated with a marked inhibition of
NF-kappaB nuclear translocation. Finally,
JM34 inhibited delayed type
hypersensitivity dose dependently in mice. In conclusion, our data suggest that
JM34 inhibited T lymphocyte activation mainly by targeting DC, and thus may represent a new class of therapeutic agents in the fields of
transplantation and
autoimmune diseases.