Human CD83 is a 40 - 50 kDa member of the Siglec (or sialic-acid-binding immunoglobulin-like lectin) family of transmembrane proteins (1, 2, 3). CD83 is synthesized as a type I transmembrane glycoprotein that contains a 125 amino acid (aa) extracellular region, a 22 aa transmembrane segment, and 39 aa cytoplasmic domain. It contains one V type Ig-like domain in the extracellular region with no inhibitory cytoplasmic motif(s). Although in vitro studies suggest CD83 may form membrane-bound covalent homodimers, in vivo this does not appear to be the case (1, 4). In the extracellular region, mouse and human CD83 are 66% aa identical (1, 2, 4, 5). Relative to human, mouse CD83 is 11 aa shorter in its extracellular domain and is expressed as a 30 - 35 kDa protein (1, 4, 5). Human CD83 is active in the mouse system (4). One alternate splice form has been reported. This leads to a small monomeric soluble form of 74 aa that includes aa’s # 20 - 52 and # 164 - 205 (6, 7). In human, proteolytic cleavage and solubilization of CD83 has also been suggested, and this could lead to dimeric circulating CD83 (4, 6). CD83 is a primary marker for dendritic cells (3, 6, 8). It is also found on B cells (6, 9), neutrophils (10), monocytes and macrophages (11). Except for dendritic cells, CD83 expression is often transient. CD83 binds to sialic acids on target cells (12). The function of CD83 is only now becoming clear. Membrane CD83 appears to promote T cell proliferation, particularly of CD8⁺ cytotoxic T cells (13, 14). Soluble CD83, however, appears to be immunosuppressive and blocks T cell activation (15, 16). On monocytes, CD83 is suggested to drive monocytes into a fibrocyte phenotype (13). A lack of membrane-expressed CD83 leads to an unusual IL-4/IL-10 producing CD4⁺ T cell phenotype (17).