Induction Of CD83 Expression Research Articles

CD83 expression regulates antibody production in response to influenza A virus infection

BackgroundCD83 is known to regulate lymphocyte maturation, activation, homeostasis, and antibody response to immunization and infection. While CD83 has a major part in B cell function, its role in influenza A virus infection has not yet been investigated.MethodsWe investigated the role of CD83 using C57BL/6J wild type mice and CD83 knockout (KO) mice after intraperitoneal administration of the influenza A/WSN/1933 virus. We analyzed cells of the peritoneal cavity, splenocytes, and cells of the bone marrow with FACS to investigate CD83 expression and cell population change in response to the virus infection. ELISA was performed with sera and peritoneal cavity fluids to detect A/WSN/1933 virus-specific IgG and the subclasses of IgG.ResultsFACS analysis data showed a transient but distinct induction of CD83 expression in the peritoneal B cells of wild type mice. CD83 KO mice exhibited a delayed recovery of B cells in the bone marrow after influenza virus infection and overall, a smaller T cell population compared to wild type mice. The peritoneal cavity and serum of the wild type mice contained a high titer of IgG within 14 days after infection, whereas the CD83 KO mice had a very low titer of IgG.ConclusionsThese results show the importance of CD83 in lymphocytes homeostasis and antibody production during influenza A virus infection.

Lack of phenotypic and functional impairment in dendritic cells from chimpanzees chronically infected with hepatitis C virus.

Dendritic cells (DCs), which are potent antigen-presenting cells (APCs), are used as adjuvants for the treatment of cancer and infectious diseases in human and nonhuman primates, with documented clinical efficacy. The hepatitis C virus (HCV)-chimpanzee model is the best available model for testing the immunotherapeutic effects of DCs in the setting of a chronic infection, as chimpanzees develop a persistent infection resembling that seen in humans. However, several reports have suggested that DCs derived from chronically infected individuals or nonhuman primates are functionally compromised. As a prelude to clinical studies, we evaluated whether functionally mature DCs could be generated in chimpanzee plasma by good manufacturing practice using CD14(+) mononuclear precursors from chronically infected chimpanzees. DCs generated in a medium with HCV-negative plasma and treated with a defined cocktail of cytokines or a CD40 ligand trimer matured fully, as measured by the induction of CD83 expression and the upregulation of costimulatory molecules. Furthermore, the expression of CCR7 was induced, suggesting an acquisition of migration capacity. Mature DCs were capable of stimulating allogeneic T cells, antigen-specific memory CD4(+) T cells, and HCV-specific CD8(+)-T-cell clones. In all cases, there was no evidence of HCV infection in DCs. Furthermore, these DCs maintained their phenotype and APC function after cryopreservation. Finally, no discernible differences were noted between DCs derived from HCV-infected and uninfected chimpanzees. In summary, precursor cells from HCV-infected chimpanzees are fully capable of differentiating into functional, mature DCs, which can now be reproducibly prepared for investigations of their immunotherapeutic potential in the setting of chronic HCV infection.

CD20 antibody (C2B8)-induced apoptosis of lymphoma cells promotes phagocytosis by dendritic cells and cross-priming of CD8+ cytotoxic T cells.

C2B8 (Rituximab, MabThera) is a chimeric mouse/human monoclonal antibody (mAb) directed against the human B cell-restricted cell surface antigen CD20 which is used as an alternative medication in the treatment of B cell non-Hodgkin lymphomas (NHL). Treatment of CD20+ B cells with C2B8 triggers different cell damaging effects including complement-dependent lysis of tumor cells, antibody-dependent cellular cytotoxicity and induction of apoptosis. Dendritic cells (DC) have recently been shown to ingest cell debris and to present associated antigens even on MHC class I molecules, a mechanism called cross-presentation. In this study, we investigated whether C2B8 treatment of lymphoma promotes the induction of CD8+ T cell responses against lymphoma cell-associated antigens via, cross-presentation. We used Daudi lymphoma cells as a model system in our studies and could demonstrate, that C2B8-treated Daudi cells undergo apoptosis, are phagocytosed by DC and induce in DC typical features of maturation; among them, the induction of CD83 expression as well as the up-regulation of prominent accessory molecules (CD40, CD86) and MHC molecules. Importantly, upon co-culture of such lymphoma cell-pulsed DC with autologous T cells, we could induce efficient cytotoxic T cell (CTL) responses against Daudi cell-associated antigens. These findings suggest that antibody treatment of tumor cells can, in addition to its direct cell damaging effects, under certain conditions, contribute to an induction of potentially protective cytotoxic T cell responses.

1,25-Dihydroxyvitamin D 3 inhibits dendritic cell differentiation and maturation in vitro

Objective Because of its potent immunosuppressive properties in vitro as well as in vivo, we studied the effect of 1,25-dihydroxyvitamin D 3 (calcitriol) on differentiation, maturation, and function of dendritic cells (DC). Materials and Methods Monocyte-derived DCs were generated with GM-CSF plus IL-4, and maturation was induced by a 2-day exposure to TNFα. DCs were derived from CD34 + progenitors using SCF plus GM-CSF plus TNFα. For differentiation studies, cells were exposed to calcitriol at concentrations of 10 − 9– 10 −7 M at days 0, 6, and 8, respectively. The obtained cell populations were evaluated by morphology, phenotype, and function. Results When added at day 0, calcitriol blocked DC differentiation from monocytes and inhibited the generation of CD1a + cells from progenitor cells while increasing CD14 + cells. Exposure of immature DCs to calcitriol at day 6 resulted in a loss of the DC-characteristic surface molecule CD1a, downregulation of the costimulatory molecules CD40 and CD80, and MHC class II expression, whereas the monocyte/macrophage marker CD14 was clearly reinduced. In addition, calcitriol hindered TNFα-induced DC maturation, which is usually accompanied with induction of CD83 expression and upregulation of costimulatory molecules. In contrast, the mature CD83 + DCs remained CD1a + CD14 − when exposed to calcitriol. The capacity of cytokine-treated cells to stimulate allogeneic and autologous T cells and to take up soluble antigen was inhibited by calcitriol. Conclusion The potent suppression of DC differentiation, the reversal of DC phenotype, and function in immature DCs, as well as the inhibition of DC maturation by calcitriol, may explain some of its immunosuppressive properties.