We investigated whether diclofenac could influence the development of antigen-presenting cells in an oxygenated cholesterol-rich environment by determining its effects on the 27-hydroxycholesterol (27OHChol)-induced differentiation of monocytic cells into mature dendritic cells (mDCs). Treatment of human THP-1 monocytic cells with diclofenac antagonized the effects of 27OHChol by attenuating dendrite formation and cell attachment and promoting endocytic function. Diclofenac inhibited the transcription and surface expression of the mDC markers of CD80, CD83, and CD88, and reduced the 27OHChol-induced elevation of surface levels of MHC class I and II molecules to the basal levels in a dose-dependent manner. It also reduced the expression of CD197, a molecule involved in DC homing and migration. These results indicate that diclofenac inhibits the differentiation of monocytic cells into mDCs, thereby potentially modulating adaptive immune responses in a milieu rich in cholesterol oxidation products.
Antigen-Presenting Cells ; Cholesterol ; Dendrites ; Dendritic Cells* ; Diclofenac* ; Humans ; Oxygen

A mysterious puzzle in immunology is how the immune system decides what types of immune response to initiate against various stimuli. Although much is known about control of T helper 1 (Th1) and Th17 responses, the mechanisms that initiate Th2 responses remain obscure. Antigen-presenting cells, particularly dendritic cells (DCs), are mandatory for the induction of a Th cell response. Numerous studies have documented the organizing role of DCs in this process. The present review summarizes the fundamental roles of DCs in inducing Th2 responses.
Allergy and Immunology ; Antigen-Presenting Cells ; Dendritic Cells* ; Immune System

Activation of T cells for an immune response requires the participation of antigen presenting cells (APC) that express class II major histocompatibility complex gene products on their surface. Until recently, the macrophages have been considered to be the prime candidates for this role, but it is now recognized that other cells, including dendritic cells, B cells, activated T cells and endothelial cells, can present antigen effectively. Particularly, among them, dendritic cells (DC) are considered to be very efficient APC for various T -cell dependent immune responses in comparison with other types of APC. Nonlymphoid dendritic cells including Langerhans cells and interstitial dendritic cells strongly express the MHC class II products and have characteristic dendritic morphology. As far as we know, there is no study on the ontogeny of MHC class II -immunoreactive dendritic cells in the rat tongue. The aim of the present study is to investigate the ontogeny and morphological characterization of dendritic cells in the tongue of growing and developing rats. The distribution and morphology of the dendritic cells in the rat tongue were studied from the fetal 15 -day until 180 days after birth by means of immunocytochemical methods using anti -rat MHC class II monoclonal antibodies. The results were as follows: 1. MHC class II -immunoreactive dendritic cells were first found in the muscle layer of 17 -day fetus, and in the epithelium and lamina propria of the tongue at birth. 2. The number of MHC class II -immunoreactive dendritic cells was gradually increased with age, particularly, in the epithelium at 14th day, in the lamina propria at 14th day, and in the muscle layer at 21st day after birth. 3. Numbers of MHC class II -immunoreactive dendritic cells were higher in the dorsal part than in ventral part of the tongue at all developmental stages. Especially, dendritic cells were twice higher numbers in the epithelium, a little higher numbers in the lamina propria and almost same numbers in the muscle layer. 4. With age, shapes of MHC class II -immunoreactive dendritic cells were changed from round to dendritic and aggregated together. In conclusion, the above results suggest that the increases of the number and the changes of the morphology in MHC class II -immunoreactive dendritic cells, with age may influence on effects of cell -mediated immune responses.
Animals ; Antibodies, Monoclonal ; Antigen-Presenting Cells ; B-Lymphocytes ; Dendritic Cells* ; Endothelial Cells ; Epithelium ; Fetus ; Growth and Development* ; Langerhans Cells ; Macrophages ; Major Histocompatibility Complex ; Mucous Membrane ; Parturition ; Rats* ; T-Lymphocytes ; Tongue*

Dendritic cells (DCs) are professional antigen-presenting cells capable of initiating and regulating innate and adaptive immunity. The development of effective ways to produce a large number of DCs in laboratories made the use of DCs available in various vaccine approaches. Compared to conventional vaccines, focused on protective antibody responses, DC vaccines emphasize protective T cell immunity but might elicit strong antibody responses as well. In addition, the recent discoveries of functionally distinct DC subsets in various organs and tissues are likely to increase the potential of exploiting DCs in vaccines and immunotherapy. Vaccines composed of DCs generated ex vivo, pulsed with antigens, and matured prior to being re-infused to the body have been widely tried clinically but resulted in limited success due to various obstacles. In this review, new approaches that protein vaccines are selectively targeted to the endocytic C-type lectin receptors on surface of DCs in vivo are discussed.
Adaptive Immunity ; Antibody Formation ; Antigen-Presenting Cells ; Dendritic Cells* ; Immunotherapy ; Lectins, C-Type* ; Receptors, Antigen ; Vaccines

BACKGROUND: Although dendritic cells (DCs) are the most influential antigen presenting cells maturation of DC is the critical control point toward either activation or regulation of immunity. We hypothesized that pretreatment with donor DCs, if which were maturation-resistant in vivo, could enhance engraftment by inducing inactivated state for allo- reactive T cell clones. METHODS: Immature DCs were prepared by 6- day culture of BM cells and we used paraformaldehyde for locking the DCs as immature phenotypes. We did in vitro and in vivo MLR to evaluate the effect of maturation resistant DCs on alloreactive T cells and we confirmed the effect of DCs in MHC full mismatched skin and islet transplantation model. RESULTS: Fixed DCs in immature state were resistant to maturation stimuli and weak stimulator for allo-reactive T cells (CB6F1-->C3H). In contrast, fixed DCs in mature state stimulated allogeneic T cell proliferation effectively. Splenocytes isolated from mice 2 weeks after maturation resistant DC injection could not be reactivated and maintained naive phenotype when cocultured with allogeneic splenocytes (BALB/c-->C57BL6). Consistent with this finding maturation resistant DC treatment suppressed MLR-driven T cell division (CB6F1-->C3H) as assessed by CFSE analysis. But, CD25+ T cells depletion by treatment with anti-CD25 prior to DCs transfer attenuated this regulatory effect of DCs. In a MHC mismatched transplantation model (CB6F1-->C3H), treatment with maturation-resistant DCs 2 weeks before operation, markedly prolonged skin and islet graft survival. But C3H mice pretreated with CB6F1 DCs rejected DBA1 (H-2q) skin graft within 14 days. CONCLUSION: These findings suggest the maintenance of immaturity of DCs is a key factor in modulating alloimmune responses through dendritic cells.
Animals ; Antigen-Presenting Cells ; Cell Division ; Cell Proliferation ; Clonal Anergy ; Clone Cells ; Dendritic Cells* ; Graft Survival ; Humans ; Islets of Langerhans Transplantation ; Mice* ; Mice, Inbred C3H ; Phenotype ; Skin ; T-Lymphocytes ; Tissue Donors* ; Transplantation Tolerance ; Transplants

CD1d expressing dendritic cells (DCs) are good glyco-lipid antigen presenting cells for NKT cells. However, resting B cells are very weak stimulators for NKT cells. Although alpha-galactosylceramide (alpha-GalCer) loaded B cells can activate NKT cells, it is not well defined whether B cells interfere NKT cell stimulating activity of DCs. Unexpectedly, we found in this study that B cells can promote Th1-skewed NKT cell response, which means a increased level of IFN-gamma by NKT cells, concomitant with a decreased level of IL-4, in the circumstance of co-culture of DCs and B Cells. Remarkably, the response promoted by B cells was dependent on CD1d expression of B cells.
Antigen-Presenting Cells ; B-Lymphocytes* ; Coculture Techniques ; Dendritic Cells ; Galactosylceramides ; Interleukin-4 ; Natural Killer T-Cells*

Dendritic cells (DCs) are crucial in the defense against pathogens and allergen. The ability of allergens to cause allergic inflammation is contingent upon the presence of microenvironment that either privileges Th2 responses or prohibits these reactions. As a simplification, this review tried to prove a causal relationship between a allergic disease and dendritic cell by satisfying the modified Koch's postulates. DCs express C-type lectin receptors (CLRs) and Toll like receptors (TLRs). DCs take up almost all allergen through CLRs. Uptake of allergen by CLRs leads to the production of anti-inflammatory reactions. Although both TLRs and CLRs have distinct functions, the balance between both receptors is instrumental for the immunological outcome.
Allergens ; Antigen-Presenting Cells ; Dendritic Cells* ; Inflammation ; Lectins, C-Type ; Toll-Like Receptors

Dendritic cells (DCs) are potent antigen-presenting cells and generated from diverse sources including monocytes which are known to be the sites for human cytomegalovirus (HCMV) latency. HCMV has been known to suppress or evade from immune functions involving monocytes and DC. Thus, it was attempted to investigate the effect of HCMV infection on the differentiation of DCs from monocytes. Monocytes were prepared from peripheral blood mononuclear cells and they expressed high levels of CD14, CD11a, CD11b, CD11c and HLA molecules, while they did not express lymphocyte-specific CD molecules. The surface expressions of CD molecules and HLA in immature DCs (imDCs) differentiated from HCMV-infected monocytes differed from those in uninfected imDCs. Specifically, the expressions of CD11a, CD11b, CD11c, CD40 and HLA-DR were decreased compared to uninfected imDCs, while CD80 expression was increased in imDCs differentiated from HCMV-infected monocytes. DCs were allowed to mature (mDCs) by treating imDCs with interferon gamma and LPS. When HCMV-infected imDCs were differentiated to mDCs, the expression of mDC-specific CD83 as well as HLA molecules were decreased. Thus, our results suggest that HCMV inhibits phenotytpic differentiation of DCs.
Antigen-Presenting Cells ; Cytomegalovirus* ; Dendritic Cells* ; HLA-DR Antigens ; Humans* ; Interferons ; Monocytes

Dendritic cells (DCs) are the most professional antigen presenting cells that play important roles in connection between innate and adaptive immune responses. Numerous studies revealed that the functions of DCs are related with the capture and processing of antigen as well as the migration to lymphoid tissues for the presenting antigens to T cells. These unique features of DCs allow them to be considered as therapeutic vaccines that can induce immune responses and anti-tumor activity. Here, we discuss and understand the immunological basis of DCs and presume the possibilities of DC-based vaccines for the promising cancer therapy.
Antigen-Presenting Cells ; Cancer Vaccines ; Dendritic Cells ; Immunotherapy ; Lymphoid Tissue ; T-Lymphocytes ; Vaccines

BACKGROUND: Cordyceps militarys water extract (CME) has been reported to exert antitumor and immunomodulatory activities in vivo and in vitro. However, the therapeutic mechanism has not yet been elucidated. In this study, we examined the effects of CME on the antigen presenting function of antigen presenting cells (APCs). METHODS: Dendritic cells (DCs) were cultured in the presence of CME, and then allowed to phagocytose microspheres containing ovalbumin (OVA). After washing and fixing the efficacy of OVA, peptide presentation by DCs were evaluated using CD8 and CD4 T cells. Also, we confirmed the protein levels of proinflammatory cytokines through western blot analysis. RESULTS: CME enhanced both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the expression of both MHC class I and II molecules was enhanced, but there was no changes in the phagocytic activity of exogenous OVA. Furthermore, CME induced the protein levels of iNOS, COX-2, proinflammatory cytokines, and nuclear p65 in a concentration-dependent manner, as determined by western blot. CONCLUSION: These results provide an understanding of the mechanism of the immuno-enhancing activity of CME on the induction of MHC-restricted antigen presentation in relation to their actions on APCs.
Antigen Presentation ; Antigen-Presenting Cells ; Blotting, Western ; Cordyceps ; Cytokines ; Dendritic Cells ; Microspheres ; Ovalbumin ; Ovum ; T-Lymphocytes ; Water