Cutting Edge: CD83 Regulates the Development of Cellular Immunity

Abstract

We recently found that human CD83, a marker of mature dendritic cells, is an adhesion receptor that binds to resting monocytes and a subset of activated CD8+ T cells. We injected CD83-Ig into mice transplanted with the immunogenic P815 mastocytoma and showed that it significantly enhanced the rate of tumor growth and inhibited the development of cytotoxic T cells. In contrast, mice immunized with CD83-transfected K1735 cells, a poorly immunogenic melanoma, could prevent the outgrowth of wild-type K1735 cells. Studies performed in vitro with human PBL showed that coimmobilized CD83-Ig and anti-CD3 enhanced T cell proliferation and increased the proportion of CD8+ T cells. CD83-transfected B-lymphoblastoid T51 cells stimulated T cell proliferation more effectively than untransfected T51 cells in MLR cultures and increased the generation of cytolytic T cells. We conclude that CD83 is a functionally important receptor that can regulate the development of cellular immunity by interacting with its ligand(s).

Phosphorylation of the HuR ligand APRIL by casein kinase 2 regulates CD83 expression

“…Although its exact function is still unknown, various independent studies using soluble forms of CD83 or employing CD83-specific RNA interference provided evidence that this surface molecule is required for efficient DC-mediated T-cell activation [14][15][16][17]19]. Furthermore, it has been shown that CD4 1 single-positive thymocyte development is impaired in CD83 (CD83 À/À ) knockout mice, resulting in pronounced reduction of peripheral CD4 1 T cells [44].…”

“…Moreover, a soluble form of CD83 is detectable at low levels in sera derived from healthy individuals, whereas in contrast, elevated levels are present in patients suffering from certain hematological malignancies [8,11]. Notwithstanding the fact that accumulating experimental evidence suggests that CD83 plays an important functional role in the regulation of DCmediated T-cell-specific immune response [12][13][14][15][16][17][18][19], the exact function of CD83 remains poorly understood [20][21][22]. Nevertheless, various disease-related findings suggest that CD83 holds great potential for future therapeutic application [23].…”

Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus

“…The precise functions of this molecule remain unknown (76,77), but CD83 may serve important roles during intercellular interactions (77)(78)(79), as membrane-bound CD83 increases the stimulatory capacity of DCs (79). Further, previous studies suggest that CD83 mediates adhesion to monocytes and CD8 ϩ T cells (80). CD83-Ig enhances T cell proliferation and increases the proportion of CD8 ϩ T cells (80), and engagement of CD83 delivers a significant signal specifically supporting the expansion, survival and function of newly primed naive CD8 ϩ T cells (81).…”

“…Further, previous studies suggest that CD83 mediates adhesion to monocytes and CD8 ϩ T cells (80). CD83-Ig enhances T cell proliferation and increases the proportion of CD8 ϩ T cells (80), and engagement of CD83 delivers a significant signal specifically supporting the expansion, survival and function of newly primed naive CD8 ϩ T cells (81). CD8 ϩ T cells in lupusprone mice are impaired in expansion, acquisition of memory, secretion of cytokine, and suppression of autoimmunity (8,82) and because CD83 appears to have a role in CD8 ϩ function, it is possible that down-regulation of the former could contribute to abnormal CD8 ϩ function in SLE.…”

CD83 Expression in CD4+ T Cells Modulates Inflammation and Autoimmunity

“…Additionally, in the experimental autoimmune encephalomyelitis (EAE) mouse model, injections of sCD83 prevented the disease-associated paralysis under prophylactic as well as therapeutic settings in vivo (21). Scholler and coworkers reported that recombinant expression of a CD83-human Ig and CD83-murine Ig fusion protein inhibited DC-mediated T cell stimulation in vitro in a concentration-dependent manner (22). Additionally, they demonstrated that sCD83 down-modulates antitumor immune responses in vivo using the murine P815 tumor model (22).…”