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In an objective to find out an effective, nontoxic dendritic cell (DC) maturating agent for human use, CD14 + monocytes were differentiated with GMCSF/IL-4 and matured with neem leaf glycoprotein (NLGP). NLGP matured DCs (NLGP-DCs) show upregulated expression of CD83, CD80, CD86, CD40 and MHCs, in a comparable extent of control, LPS. NLGP-DCs secrete high amount of IL-12p70 with low IL-10...
We have previously shown that Toll-like receptor (TLR) agonists cooperate with CD40 to generate CD8 T cell responses exponentially larger than the responses generated with traditional vaccine formulations. We have also shown that combined TLR agonist/anti-CD40 immunization uniquely induces the upregulation of CD70 on antigen bearing dendritic cells (DCs). In contrast, immunization with either a TLR...
Effective induction of cell-mediated immune responses strongly depends on the ability of dendritic cells (DCs) to produce Th1-polarizing cytokines, migrate to lymph nodes and stimulate T cells through antigen-presenting complex and costimulatory molecules. While various protocols for optimizing DC maturation with single or multiple stimuli mimicking infections or inflammatory milieu have been proposed...
Engagement of CD40 with CD40L induces dendritic cell (DC) maturation and activation, thereby promoting immune responses. The objective of this study was to investigate whether immunization with chimeric CD40L/SHIV virus-like particles (CD40L/SHIV-VLP) could enhance immune responses to SIV Gag and HIV Env proteins by directly activating DCs. We found that CD83, CD40, and CD86 were significantly up-regulated...
We had isolated a high molecular weight polysaccharide fraction, designated as F3, and performed a comprehensive analysis of its immunomodulatory and adjuvant activities in vivo and in vitro. In vivo, F3-treated mice showed an increase in the number of dendritic cells as well as CD4, CD8, regulatory T, B, plasma, NK, and NKT cells in the spleen. F3 also elevated the levels of multiple cytokines and...
Dendritic cells form the connection between innate and adoptive mechanisms of the immune system. As antigen-presenting cells, dendritic cells are capable of presenting tumour antigen and effectively stimulating immune response targeted against a tumour. A number of preclinical and clinical studies document dendritic cells’ potential in anti-cancer treatment. Increasing knowledge of dendritic cell...
The Ligand Epitope Antigen Presentation System (LEAPS) converts a peptide containing a T cell epitope as small as 8 amino acids into an immunogen and directs the nature of the subsequent response. Tandem synthesis of the J peptide (a peptide from the beta-2-microglobulin) with peptides of 15 or 30 amino acids from HSV-1 or HIV made them immunogenic and promoted Th1 immune responses. Immunization of...
The purpose of this in vitro study was to determine if a virus-like particle (VLP) influenza vaccine stimulated human CD8 + T cells in a dendritic cell (DC): T cell co-culture system. VLP-pulsed DCs were co-cultured with autologous CD8 + T cells from five donors. Functional CD8 + T cells were detected via cell surface and intracellular cytokine staining. T cells from four of...
We have evaluated whether cholera toxin (CT) as a carrier/adjuvant can enhance human T-cell responses to a viral oncoprotein in vitro using dendritic cells (DCs) as antigen-presenting cells. Monocyte-derived DCs obtained from women with cervical dysplasia were pulsed with the HPV16 oncoprotein E7, either alone or conjugated to CT, and tested for their ability to induce antigen-specific activation...
Upon loading with parasite antigen and adoptive transfer, dendritic cells (DC) are able to confer protection against the protozoan parasite Leishmania major. In the present study, we investigated whether viable DC are required for inducing protection. We provide evidence that L. major antigen-loaded DC that had been fixed with paraformaldehyde or exposed to UV irradiation, and even disrupted cells,...
Aluminium adjuvants are potent enhancers of immune responses. Despite being a component in most human and animal vaccines, their specific mode of action remains elusive. We have used a sheep lymphatic cannulation model to directly measure the trafficking of soluble and particulate antigen in real-time from the site of injection. Aluminium adjuvant does not alter the kinetics of antigen flow from the...
Recent evidence suggested that angiogenesis played a pivotal role in the development of hepatocellular carcinoma cells (HCC), thus the therapy strategy targeting antiangiogenesis has been regarded as promising method for HCC therapy. Tumor endothelial marker 8 (TEM8) is a recently described protein that is preferentially expressed within tumor endothelium. However, the antiangiogenesis therapy of...
Staphylococcus epidermidis releases a complex of at least four peptides, termed phenol-soluble modulins (PSM), which stimulate macrophages to produce proinflammatory cytokines via activation of TLR2 signalling pathway. We demonstrated that covalent linkage of PSM peptides to an antigen facilitate its capture by dendritic cells and, in combination with different TLR ligands, can favour the in vivo...
In diverse models of microbial infections, protection is improved by immunization with dendritic cells (DC) loaded with whole pathogen lysate. However, pathogens that modulate DC function as a way to evade immunity may represent a challenge for these vaccination strategies. Thus, DC must be instructed in a particular manner to circumvent this issue and drive an effective immune response. Trypanosoma...
There is a need for new adjuvants that will induce immune responses to subunit vaccines. We show that a short peptide, named Hp91, whose sequence corresponds to an area within the endogenous molecule high mobility group box (HMGB1) protein 1 potentiates cellular immune responses to peptide antigen and cellular and humoral immune responses to protein antigen in vivo. Hp91 promoted the in vivo production...
Immunoglobulin A (IgA), the most abundant Ig isotype in the body under steady-state conditions, helps to protect the body from mucosally transmitted pathogens and to maintain the homeostasis of commensal bacteria at the mucosal surface. Although it is well known that IgA is predominantly produced in mucosa-associated lymphoid tissues (MALT), little is known about why IgA class switch recombination...
Recombinant adeno-associated virus (rAAV) is being tested as a vaccine vector, but the cellular immune responses elicited in animal tumor models have not been completely protective. The adjuvant effects of the TLR7 agonist, imiquimod, and the TLR9 agonist, ODN1826, were tested with rAAV expressing the melanoma antigen, Trp2. Mice immunized with rAAV-TRP2 and either TLR agonist alone generated T-helper-1...
Immune adjuvant is an artificial pathogen-associated molecular patterns (PAMP) for potentiating various immune responses. Vaccine represents one event that is capable of inducing immune response caused by antigen and PAMP stimuli, which act on antigen-presenting dendritic cells (mDCs). Here, we introduce the pathways by which CTL and NK cells are driven through mDC maturation in response to adjuvants.
Pancreatic-islet transplantation is currently regarded as the only approach to cure type 1 diabetic patients (T1D). However, recurrent autoimmunity is a critical factor contributing to graft rejection along with alloreactivity. Recently, the glutamic acid decarboxylase 65 (GAD65) was identified as the one of the major pancreatic antigens targeted by self-reactive T cells in T1D. Therefore, the T cells...
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