CD83 has been known for a decade to be one of the best markers for mature dendritic cells (DCs). The recognition of CD83 was greatly changed since CD83 in thymus was unveiled to be essential for the generation of CD4+ T cells by the study using CD83-deficient mice. It was recently shown that both activated DCs and B cells release soluble form of CD83 and that low levels of soluble CD83 are present in normal human sera. Both in vivo and in vitro studies demonstrated that soluble CD83 has immunosuppressive roles such as the inhibition of DC-mediated T cell stimulation and the maturation of DCs. CD83 appears to have regulatory functions for immune response in light of observations that the soluble form of CD83 can inhibits immune reactions while being strongly up-regulated during DC maturation and activation. In addition, the fact that various cell types including thymic epithelial cells, activated T and B cells and activated DCs express CD83 suggests the universal role in immune function. Because of these immuno-regulatory functions, the therapeutic application of CD83 is highly anticipated in many pathological states including malignancy and autoimmune disease.