We previously demonstrated that Bordetella bronchiseptica (B. bronchiseptica) antigen (Ag) enhances the Mycoplasma hyopneumoniae Ag-specific immune response. The focus of this study was whether acellular bacterin of B. bronchiseptica could be used as an adjuvant to increase antigen-presenting capability of dendritic cells (DCs) by increasing the level of activation. The metabolic activity of DCs was increased by B. bronchiseptica, similar to lipopolysaccharide (LPS). Flow cytometry analysis revealed that B. bronchiseptica increases the expression of major histocompatibility complex class-2, cluster of differentiation (CD)40, CD54, and CD86 which are closely related to DC-mediated immune responses. B. bronchiseptica enhanced the production of cytokines related to adaptive immune responses. Furthermore, the survival rate of B. bronchiseptica-injected groups was 100% at 15 and 20 mg/kg doses, whereas that of LPS-injected groups was only 20%, 0% at 15 and 20 mg/kg doses respectively, and so B. bronchiseptica is likely to be safer than LPS. Taken together, these results indicate that B. bronchiseptica can be used as an adjuvant to enhance the antigen-presenting capability of DCs. B. bronchiseptica is a candidate for producing vaccines, especially in case of DC-mediating efficacy and safety demands. This study provides researchers and clinicians with valuable information regarding the usage of B. bronchiseptica as a safe bacteria-derived immunostimulating agent for developing efficient vaccines.
Bacterial Vaccines ; Bordetella bronchiseptica ; Bordetella ; Cytokines ; Dendritic Cells ; Flow Cytometry ; Immunization ; Major Histocompatibility Complex ; Mycoplasma hyopneumoniae ; Survival Rate ; Vaccines

Despite their being uncommon, severe cutaneous adverse drug reactions (SCARs) result in a very great burden of disease. These reactions not only carry with them a high mortality (10%–50%) and high morbidity (60%) with severe ocular complications, alopecia, oral and dental complications and development of autoimmune diseases, but also create a substantial economic burden for patients' families and society. SCARs are, therefore, an important medical problem needing a solution in many countries, especially in Asia. The clinical spectrum of SCARs comprises Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS (drug rash with eosinophilia and systemic symptoms) (also known as drug hypersensitivity syndrome or drug-induced hypersensitivity syndrome) and acute generalised exanthematous pustulosis. Recent crucial advances in determining genetic susceptibility and understanding how T cells recognise certain medications or their metabolites via the major histocompatibility complex and the effects of cofactors, have led to the implementation of cost-effective screening programs enabling prevention in a number of countries, and to further understanding of the patho-mechanisms involved in SCARs and their significance. In this review, we document comprehensively the journey of SCARs from bedside to bench and outline future perspectives in SCARs research.
Alopecia ; Asia ; Autoimmune Diseases ; Cicatrix ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions ; Eosinophilia ; Exanthema ; Genetic Predisposition to Disease ; Humans ; Hypersensitivity ; Leukocytes ; Major Histocompatibility Complex ; Mass Screening ; Mortality ; Stevens-Johnson Syndrome ; T-Lymphocytes

Long-term maintenance of transplanted organs is one of the major factors that increases survival time of recipients. Although obtaining a major histocompatibility complex (MHC)-matched donor with the recipient is essential for successful organ transplantation, there have been limited reports on MHC matching between dogs. In this study, we analyzed the canine MHC matching rates using Maltese, one of the most popular purebred dogs, and mongrel dogs in Korea. Genomic DNA was extracted from blood leukocytes and DNA was amplified by polymerase chain reaction with primers specific to MHC microsatellite markers. The MHC matching degree was confirmed by the microsatellite markers using polyacrylamide gel electrophoresis. The MHC matching rates of each donor-recipient groups including Maltese-Maltese, mongrel-mongrel and Maltese-mongrel were 4.76%, 5.13% and 6.67%, respectively. There were no significant differences in the MHC matching degree between each group. These results demonstrate that MHC-matched donors could be selected from other breeds as much as from the same breed for transplantation. Knowledge of the MHC matching degree of purebred and mongrel dogs would offer valuable information not only for improving the success rate of organ transplantation surgery in canine patients but also for transplantation research using experimental canine models.
Animals ; DNA ; Dogs ; Electrophoresis, Polyacrylamide Gel ; Humans ; Korea ; Leukocytes ; Major Histocompatibility Complex ; Microsatellite Repeats ; Organ Transplantation ; Polymerase Chain Reaction ; Tissue Donors ; Transplants

PURPOSE: Vitamin D is a potent immunomodulator. However, its role in the pathogenesis of allergic rhinitis is unclear. METHODS: The aim of this study was to evaluate the antiallergic effect of intranasally applied vitamin D in an allergic rhinitis mouse model. BALB/c mice were intraperitoneally sensitized with ovalbumin (OVA) and alum before they were intranasally challenged with OVA. Then, they were intranasally administered 1, 25-dihydroxyvitamin D3 (0.02 μg) or solvent. Allergic symptom scores, eosinophil infiltration, cytokine mRNA levels (interleukin [IL]-4, IL-5, IL-10, IL-13 and interferon-γ) in the nasal tissue, and serum total immunoglobulin E (IgE) and OVA-specific IgE, IgG1, and IgG2a were analyzed and compared with negative and positive control groups. Cervical lymph nodes (LNs) were harvested for flow cytometry analysis and cell proliferation assay. RESULTS: In the treatment group, allergic symptom scores, eosinophil infiltration, and mRNA levels of IL-4 and IL-13 were significantly lower in the nasal tissue than in the positive control group. The IL-5 mRNA level, serum total IgE, and OVA-specific IgE and IgG1 levels decreased in the treatment group; however, the difference was not significant. In the cervical LNs, CD86 expression had been down-regulated in CD11c+major histocompatibility complex II-high (MHCIIhigh) in the treatment group. Additionally, IL-4 secretion in the lymphocyte culture from cervical LNs significantly decreased. CONCLUSIONS: The results confirm the antiallergic effect of intranasal 1,25-dihydroxyvitamin D3. It decreases CD 86 expression among CD11c+MHCIIhigh cells and T-helper type 2-mediated inflammation in the cervical LNs. Therefore, topically applied 1,25-dihydroxyvitamin D3 can be a future therapeutic agent for allergic rhinitis.
Administration, Intranasal ; Animals ; Anti-Allergic Agents ; Calcitriol ; Cell Proliferation ; Dendritic Cells ; Eosinophils ; Flow Cytometry ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Inflammation ; Interleukin-10 ; Interleukin-13 ; Interleukin-4 ; Interleukin-5 ; Lymph Nodes ; Lymphocytes ; Major Histocompatibility Complex ; Mice ; Models, Animal ; Ovalbumin ; Ovum ; Rhinitis, Allergic ; RNA, Messenger ; Vitamin D

BACKGROUND: Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear. METHODS: We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed. RESULTS: Total loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II–IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I–positive tumors than in HLA-I–negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort. CONCLUSIONS: Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.
Breast Neoplasms ; Breast ; Cohort Studies ; HLA Antigens ; Humans ; Immune Evasion ; Immunohistochemistry ; Immunotherapy ; Leukocytes ; Lymphocytes, Tumor-Infiltrating ; Major Histocompatibility Complex ; Prognosis ; T-Lymphocytes, Regulatory

BACKGROUND: Human embryonic stem cells (hESCs) have the potential to treat various human disorders currently labeled as incurable and/or terminal illness. However, the fear that the patients' immune system would recognize them as non self and lead to an immune rejection has hampered their use. The main cause for immune rejection is usually the incompatibility of both donor and recipient's major histocompatibility complex (MHC). METHODS: We describe a hESC line developed through a patented technology that does not lead to immune reaction upon transplantation. We have transplanted these cells in >1,400 patients with chronic/terminal conditions and did not observe any immune reaction. No immunosuppressant were administered to these patients. We analyzed the expression levels of MHC-I and MHC-II on the surface of these hESCs using microarray technology. The gene targets for miRNA were analyzed using Gene ontology and DAVID database and pathways for these genes were determined using Reactome and Panther databases. RESULTS: Our results showed that the levels of expression of MHC-I and MHC-II on hESCs is almost negligible and thus the hESCs are less susceptible to an immune rejection. CONCLUSIONS: The hESCs cultured at our facility expresses low levels of MHC-I and do not produce an immune reaction. These can be administered universally and need no cross matching before transplantation.
Cell Line ; Gene Ontology ; Human Embryonic Stem Cells ; Humans ; Immune System ; Major Histocompatibility Complex ; MicroRNAs ; Neurons ; Tissue Donors ; Zygote

B cells play a role in graft rejection via several mechanisms. Specifically, B cells produce high-affinity antibodies to alloantigens including allogeneic major histocompatibility complex (MHC) with the help of follicular helper T cells. B cells also function as antigen-presenting cells for alloreactive T cells, resulting in the activation of alloreactive T cells. Conversely, the frequency of regulatory B cells increases under inflammatory conditions and suppresses the rejection process. Here, the differential roles of the major B cell subpopulations (B-1, follicular B, marginal zone B, and regulatory B cells) involved in transplantation rejection are discussed together with their interaction with T cells.
Antibodies ; Antibody Diversity ; Antigen-Presenting Cells ; B-Lymphocytes* ; B-Lymphocytes, Regulatory ; Graft Rejection* ; Isoantigens ; Major Histocompatibility Complex ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer

Bone marrow-derived dendritic cells (BM-DCs) are generated from bone marrow (BM) cells cultured with granulocyte macrophage-colony stimulating factor (GM-CSF) for a week. In this study we investigated the effect of duration on the BM culture with GM-CSF. Within several months, the cells in the BM culture gradually expressed homogeneous levels of CD11c and major histocompatibility complex II on surface, and they became unable to stimulate allogeneic naïve T cells in mixed lymphocyte reaction (MLR). In addition, when the BM culture were sustained for 32 wk or longer, the BM cells acquired ability to suppress the proliferation of allogeneic T cells in MLR as well as the response of ovalbumin-specific OT-I transgenic T cells in antigen-dependent manner. We found that, except for programmed death-ligand 1, most cell surface molecules were expressed lower in the BM cells cultured with GM-CSF for the extended duration. These results indicate that BM cells in the extended culture with GM-CSF undergo 2 distinct steps of functional change; first, they lose the immunostimulatory capacity; and next, they gain the immunosuppressive ability.
Bone Marrow* ; Dendritic Cells ; Granulocyte-Macrophage Colony-Stimulating Factor ; Granulocytes* ; Immunosuppression ; Lymphocyte Culture Test, Mixed ; Major Histocompatibility Complex ; T-Lymphocytes

PURPOSE: The use of tolerogenic dendritic cells (TolDCs) to control exacerbated immune responses may be a prophylactic and therapeutic option for application in autoimmune and allergic conditions. The objective of this work was to evaluate the effects of TolDC administration in a mouse model of allergic airway inflammation caused by mite extract. METHODS: Mouse bone marrow-derived TolDCs were induced by incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) and dexamethasone, and then characterized by flow cytometry and cytokine production by enzyme-linked immunosorbent assay (ELISA). For the in vivo model of Blomia tropicalis-induced allergy, mice transplanted with antigen-pulsed TolDCs were sensitized intraperitoneally with B. tropicalis mite extract (BtE) adsorbed to aluminium hydroxide. After challenge by nasal administration of BtE, bronchoalveolar lavage fluid (BALF), lungs, spleen and serum were collected for analysis. RESULTS: Induction of TolDCs was efficiently achieved as shown by low expression of major histocompatibility complex (MHC) II, programmed death-ligand (PD-L) 2 and pro-inflammatory cytokine production, and up-regulation of interleukin (IL)-10, upon LPS stimulation in vitro. Transplantation of 1 or 2 doses of BtE-pulsed TolDCs reduced the number of inflammatory cells in BALF and lungs as well as mucus deposition. Moreover, compared to saline-injected controls, TolDC-treated mice showed lower serum levels of anti-BtE immunoglobulin E (IgE) antibodies as well as reduced Gata3 and IL-4 gene expression in the lungs and decreased IFN-γ levels in the supernatant of splenocyte cultures Transplantation of TolDCs increased the percentage of the regulatory T cells in the spleen and the lungs. CONCLUSIONS: Preventive treatment with TolDCs protects against dust mite-induced allergy in a mouse model, reinforcing the use of tolerogenic dendritic cells for the management of allergic conditions.
Administration, Intranasal ; Animals ; Antibodies ; Antigens, Dermatophagoides ; Asthma ; Bronchoalveolar Lavage Fluid ; Dendritic Cells* ; Dexamethasone ; Dust* ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Gene Expression ; Granulocyte-Macrophage Colony-Stimulating Factor ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulins ; In Vitro Techniques ; Inflammation* ; Interleukin-4 ; Interleukins ; Lung ; Major Histocompatibility Complex ; Mice ; Mites* ; Mucus ; Spleen ; T-Lymphocytes, Regulatory ; Up-Regulation

IL-9 is a known T cell growth factor with pleiotropic immunological functions, especially in parasite infection and colitis. However, its role in tumor growth is controversial. In this study, we generated tumor clones expressing the membrane-bound form of IL-9 (MB-IL-9) and investigated their influences on immune system. MB-IL-9 tumor clones showed reduced tumorigenicity but shortened survival accompanied with severe body weight loss in mice. MB-IL-9 expression on tumor cells had no effect on cell proliferation or major histocompatibility complex class I expression in vitro. MB-IL-9 tumor clones were effective in amplifying CD4⁺ and CD8⁺ T cells and increasing cytotoxic activity against CT26 cells in vivo. We also observed a prominent reduction in body weights and survival period of mice injected intraperitoneally with MB-IL-9 clones compared with control groups. Ratios of IL-17 to interferon (IFN)-γ in serum level and tumor mass were higher in mice implanted with MB-IL-9 tumor clones than those observed in mice implanted with control cells. These results indicate that the ectopic expression of the MB-IL-9 on tumor cells exerts an immune-stimulatory effect with toxicity. To exploit its benefits as a tumor vaccine, a strategy to control the toxicity of MB-IL-9 tumor clones should be developed.
Animals ; Body Weight ; Cell Proliferation ; Clone Cells ; Colitis ; Colon ; Ectopic Gene Expression ; Immune System ; In Vitro Techniques ; Interferons ; Interleukin-17 ; Interleukin-2 ; Interleukin-9 ; Major Histocompatibility Complex ; Mice ; Parasites ; T-Lymphocytes