OBJECTIVEThis review focuses on the current knowledge on the implication and significance of beta 2 microglobulin (β2M), a conservative immune molecule in vertebrate.

DATA SOURCESThe data used in this review were obtained from PubMed up to October 2015. Terms of β2M, immune response, and infection were used in the search.

STUDY SELECTIONSArticles related to β2M were retrieved and reviewed. Articles focusing on the characteristic and function of β2M were selected. The exclusion criteria of articles were that the studies on β2M-related molecules.

RESULTSβ2M is critical for the immune surveillance and modulation in vertebrate animals. The dysregulation of β2M is associated with multiple diseases, including endogenous and infectious diseases. β2M could directly participate in the development of cancer cells, and the level of β2M is deemed as a prognostic marker for several malignancies. It also involves in forming major histocompatibility complex (MHC class I or MHC I) or like heterodimers, covering from antigen presentation to immune homeostasis.

CONCLUSIONSBased on the characteristic of β2M, it or its signaling pathway has been targeted as biomedical or therapeutic tools. Moreover, β2M is highly conserved among different species, and overall structures are virtually identical, implying the versatility of β2M on applications.

Antigens, CD1 ; physiology ; Hemochromatosis Protein ; analysis ; Histocompatibility Antigens Class I ; physiology ; Humans ; Receptors, Fc ; physiology ; beta 2-Microglobulin ; blood ; chemistry ; deficiency ; physiology

OBJECTIVETo explore the clinicopathologic features, immunophenotype, differential diagnosis and gene mutation status of the Erdheim-Chester disease (ECD).

METHODSClinical and pathologic findings of 3 ECD cases were examined by gross, microscopic, immunohistochemical methods and BRAF V600E mutation. Related literatures were reviewed.

RESULTSTwo male patients and one female patient presented clinically with multiple skin nodules, bone pain and bony lesions by imaging study. Microscopically, the lesions were composed of spindle-shaped fibroblasts, foamy histiocytes and scattered Touton-type giant cells embedded in reactive fibrous tissue. Lymphocytes, plasma cells, and multinucleated giant cells were also found. Immunohistochemically, all histiocytes were positive for CD68, none of which expressed CD1a, although 2 cases focally expressed weak S-100 stain. In 2 cases,BRAF V600E mutation was detected.

CONCLUSIONSECD is a rare disease of xanthogranulomatous histiocytosis.Its diagnosis relies on pathological and immunohistochemical findings, but correlation with clinical information, especially radiographic findings should be performed.No effective treatment of the disease is currently available.

Antigens, CD ; analysis ; Antigens, CD1 ; analysis ; Antigens, Differentiation, Myelomonocytic ; analysis ; Diagnosis, Differential ; Erdheim-Chester Disease ; genetics ; immunology ; pathology ; Female ; Humans ; Male ; Mutation ; S100 Proteins ; analysis ; Treatment Outcome

OBJECTIVETo study the changes of IL-12 produced by dendritic cells in peripheral blood in children with Henoch-Schonlein purpura (HSP), and to explore its influence on TH1/TH2 balance in order to elucidate its significance in the pathogenesis of HSP.

METHODSThe levels of interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and interleukin-12 (IL-12) in plasma were determined by ELISA in 60 HSP children (HSP group) and 21 healthy children (Control group). Peripheral blood mononuclear cells (PBMC) of 22 HSP patients and 21 healthy children were cultured in vitro and then were transformed into dendritic cells. The levels of IL-12 in the supernatant were detected by ELISA and the positive expression rate of CD1a(+) was detected by indirect immunofluorescence procedure.

RESULTS1) The levels of IFN-gamma and the ratio of IFN-gamma/IL-4 in plasma of the HSP group were lower than those of the Control group (IFN-gamma 30.59 +/- 11.27 pg/mL vs 43.38 +/- 19.19 pg/mL; IFN-gamma/IL-4 ratio 0.70 +/- 0.28 vs 1.33 +/- 0.57) (P < 0.01). The levels of IL-12 in the HSP group were also lower than those of the Control group (153.95 +/- 91.88 pg/mL vs 323.06 +/- 162.34 pg/mL; P < 0.01). In contrast, the levels of IL-4 were higher than those of the Control group (45.08 +/- 9.19 pg/mL vs 32.95 +/- 7.10 pg/mL; P < 0.01). The plasma levels of IL-12 positively correlated with the IFN-gamma levels (r=0.52, P < 0.01) and the ratio of IFN-gamma/IL-4 (r=0.43, P < 0.01) in the HSP group. 2) The IL-12 levels in the supernatant of the HSP group were lower than those of the Control group (357.06 +/- 153.56 pg/mL vs 489.80 +/- 213.45 pg/mL; P < 0.05), and had a positive correlation with the plasma IL-12 levels (r=0.74, P < 0.01). 3) The positive expression rate of CD1a(+) of the HSP group was lower than that of the Control group [(27.42 +/- 10.75)% vs (35.68 +/- 12.18)%; P < 0.05], and positively correlated with the IL-12 levels in the supernatants (r=0.57, P < 0.01) and in plasma (r=0.68, P < 0.01).

CONCLUSIONSThere was an imbalance of TH1/TH2 in HSP children. The decrease of TH1 function had a positive correlation with the low levels of IL-12 in plasma, while the latter correlated closely with decreased number and / or function of dendritic cells, suggesting that the decreased number and / or function of dendritic cells in peripheral blood resulted in the imbalance of TH1/TH2 indirectly.

Adolescent ; Antigens, CD1 ; analysis ; Cells, Cultured ; Child ; Child, Preschool ; Dendritic Cells ; immunology ; Female ; Humans ; Interferon-gamma ; blood ; Interleukin-12 ; biosynthesis ; blood ; Interleukin-4 ; blood ; Male ; Purpura, Schoenlein-Henoch ; immunology ; Th1 Cells ; immunology ; Th2 Cells ; immunology

It has been suggested that dendritic cells (DCs) are critical antigen presenting cells for eosinophilic airway inflammation in a mouse model of asthma, and cysteinyl leukotrienes may play a role in DC trafficking in asthmatics. We investigated whether the number of DCs is increased in the induced sputum of both atopic and nonatopic asthmatics and is related to activated eosinophil count in the sputum. Sputum was induced by inhalation of hypertonic saline in 9 atopic and 12 nonatopic asthmatics and 10 nonatopic normal controls, and differential cell counts were performed. DCs and activated eosinophils were identified by immunocytochemistry with monoclonal antibodies (anti-CD1a and EG2, respectively). There were significantly higher percentages of eosinophils, EG2+ cells, and CD1a+ DC in the sputum of atopic and nonatopic asthmatics compared with normal controls, respectively. In asthmatics, the percentage of CD1a+ DC was significantly correlated with that of EG2+ cells (Rs=0.62, p=0.004). We demonstrated that the increased number of DCs was evident in the induced sputum of both atopic and nonatopic asthmatics, and the DC number was related to the activated eosinophil count, which suggests that DCs may contribute to the ongoing eosinophilic inflammation in asthmatic airways, and vice versa.
Adult ; Aged ; Antigens, CD1/analysis ; Asthma/*immunology/pathology ; Comparative Study ; Dendritic Cells/*immunology ; Eosinophil Granule Proteins/analysis ; Eosinophils/cytology/*immunology ; Female ; Humans ; Immunohistochemistry ; Leukocyte Count ; Male ; Middle Aged ; Research Support, Non-U.S. Gov't ; Sputum/cytology/*immunology

This study was aimed to investigate and compare the anti-leukemic effect mediated by dendritic cells (DC) derived from multidrug resistant (MDR) leukemia K562/A02 cells with high expression of p-glycoprotein (P-gp) and sensitive K562 cells. Multidrug resistant K562/A02 cell line and sensitive K562 cell line from chronic myeloid leukemia (CML) were induced for differentiating to DC in complete RPMI 1640 culture medium supplemented with GM-CSF (1 000 U/ml), IL-4 (500 U/ml) and TNF-alpha (100 ng/ml) for 14 days. The morphologic features of DC were observed by means of optical microscopy and the phenotype of DC was detected by flow cytometry. T-cell stimulating activity was determined by allogeneic lymphocyte reaction (allo-MLR). Cytotoxic activity was measured by MTT assay. The results indicated that DC derived from K562/A02 cells and K562 cells similarly showed the typical morphology of dendritic cell and expressed the surface differentiation antigens and costimulatory molecules CD1a, CD83, HLA-DR, CD80 and CD86 of DC. In allo-MLR, K562/A02-DC had a higher capacity to induce lymphocyte proliferation, compared with K562-DC (P < 0.05). K562/A02-DC and K562-DC could similarly generate specific cytotoxic activity against K562/A02 cells or K562 cells respectively, but low reactivity against HL-60 cells. More importantly, the cytotoxic activity mediated by K562/A02-DC was stronger than that by K562-DC against K562/A02 cells or HL-60/VCR cells (P < 0.01, respectively). It is concluded that functional DC can be differentiated from multidrug resistant leukemia K562/A02 cells as well as sensitive K562 cells in the presence of GM-CSF, IL-4 and TNF-alpha. Especially, DC derived from K562/A02 cells can induced a p-glycoprotein specific anti-leukemic immunity.
ATP-Binding Cassette, Sub-Family B, Member 1 ; biosynthesis ; Antigens, CD ; analysis ; Antigens, CD1 ; analysis ; B7-1 Antigen ; analysis ; B7-2 Antigen ; analysis ; Cell Differentiation ; drug effects ; immunology ; Cytotoxicity, Immunologic ; Dendritic Cells ; cytology ; immunology ; metabolism ; Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Flow Cytometry ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Humans ; Immunoglobulins ; analysis ; Interleukin-4 ; pharmacology ; K562 Cells ; Leukemia ; immunology ; pathology ; Membrane Glycoproteins ; analysis ; Tumor Necrosis Factor-alpha ; pharmacology

OBJECTIVETo elucidate the functional status of dendritic cells (DC) in the tissue of oral squamous cell carcinoma by analyzing characteristic phenotype of them.

METHODS34 specimens from oral squamous cell carcinoma cases primarily treated with surgery were selected as test group. In addition, 30 specimens of normal mucosa from oral mucocele cases were used as control. Distribution of DC expressing CD1a+, HLA-DR+ and CD83+ in tumor tissue and normal mucous membrane was observed by immunohistochemistry. The number of DC expressing the antigens, which represented the density of DC infiltrating into tissue, was counted by microscope. The density of DC and the rate of DC expressing HLA-DR in oral carcinoma group and control were statistically compared.

RESULTSThere was no CD83+ DC in all cases, but CD1a+ DC was found in all samples. The density of CD1a+ DC in tumor tissue was significantly lower than that in normal mucous membrane (P < 0.05). HLA-DR antigen expressed on the surface of DC in tumoral epithelium of 27-case carcinoma specimens and in normal mucous epithelium of 23 cases. The rate of HLA-DR positive expression of TIDC had no statistic significance between the two groups.

CONCLUSIONThe lower density of DC infiltrating in tumor tissue might reflect the microenviromental immunodeficiency of hosts with oral squamous cell carcinoma, and the functional mature of DC might be inhibited by the immunosuppressive action of oral squamous cell carcinoma.

Adult ; Aged ; Antigens, CD ; Antigens, CD1 ; analysis ; Carcinoma, Squamous Cell ; immunology ; pathology ; Cell Count ; Dendritic Cells ; immunology ; metabolism ; Female ; HLA-DR Antigens ; analysis ; Humans ; Immunoglobulins ; analysis ; Immunohistochemistry ; Male ; Membrane Glycoproteins ; analysis ; Middle Aged ; Mouth Mucosa ; immunology ; pathology ; Mouth Neoplasms ; immunology ; pathology ; Phenotype

OBJECTIVEIt is well known that vitamin A can improve mucosal immunity and anti-infection immunity. But the mechanisms thereof remain to be clarified. Previous studies on the role of vitamin A in immune regulation focused on lymphocytes, whereas little had been done about dendritic cells, which play very important roles in immune response. The objective of this study was to understand the effects of retinoic acid (RA), the metabolic product of vitamin A in vivo,on the differentiation, maturation and functions of dendritic cells from cord blood.

METHODSCord blood samples were collected from nine well-nourished full-term neonates. Mononuclear cells were isolated by Ficoll-Hypaque gradient centrifugation and cultured in the presence of 1000 u/ml GM-CSF, 500 u/ml IL-4 for 6 days, then TNF-alpha 20 ng/ml was added into the medium and cultured for another 3 days. The cells were incubated with or without 1 x 10(-6) MRA. Expression of surface molecules, CD1a, CD83, HLA-DR on DC was measured by flow cytometry. The ability of DC derived from the culture to induce proliferation of T cells in the mixed lymphocyte reaction (allo-MLR) was used for the evaluation of their function. IL-12, IFN-gamma, IL-4 and IL-10 were detected at mRNA levels by RT-PCR to understand the roles of DC treated with RA in regulation of Th1/Th2 balance.

RESULTSOn the sixth day of cell culture, the percentage of DC incubated with RA (57.28 +/- 9.22) was much lower than that without RA (79.57 +/- 11.85) (P < 0.001), but on the ninth day, there were no differences between the presence or absence of RA (76.18 +/- 10.27 vs. 73.72 +/- 15.58). When RA was added to the medium and the culture was continued for nine days, the percent of immature DC (CD1a + HLA-DR+) was much higher than that of the control (absence of RA) (58.93 +/- 4.70 vs. 45.80 +/- 7.88, t = 6.575, P < 0.001); whereas, mature DC (CD83 + HLA-DR+) percentage was markedly lower than that of the control (17.25 +/- 8.49 vs. 27.92 +/- 13.94, t = 4.435, P = 0.002). The T lymphocytes proliferation induced by the DC treated with RA was reduced from 16 857 +/- 3 643 to 11 924 +/- 2 576 cpm (t = 5.598, P < 0.001) in allo-MLR. Expression of mRNA for IL-12p35, IL-12p40, IFN-gamma in the cells that had been incubated with RA declined, but IL-10, IL-4 increased significantly.

CONCLUSIONVitamin A inhibited the differentiation and maturation of cord blood DC, reduced it's ability to stimulate allo-T lymphocytes proliferation, and down-regulated Th1 cytokines, up-regulated Th2 cytokines, consequently made immune response inclined to Th2.

Antigens, CD ; Antigens, CD1 ; analysis ; Cell Differentiation ; drug effects ; genetics ; immunology ; Cytokines ; genetics ; Dendritic Cells ; drug effects ; immunology ; metabolism ; Fetal Blood ; cytology ; immunology ; Flow Cytometry ; Gene Expression ; drug effects ; HLA-DR Antigens ; analysis ; Humans ; Immunoglobulins ; analysis ; Interferon-gamma ; genetics ; Interleukin-10 ; genetics ; Interleukin-12 ; genetics ; Interleukin-4 ; genetics ; Membrane Glycoproteins ; analysis ; Reverse Transcriptase Polymerase Chain Reaction ; Vitamin A ; pharmacology

OBJECTIVETo explore the influences of anti-CD47 monoclonal antibody (mAb) B6H12 on the differentiation and function of cultured dendritic cells (DCs).

METHODSHuman peripheral monocyte derived DCs were propagated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and lipopolysaccharide (LPS) plus interleukin-4 (IL-4) in the presence or absence of soluble B6H12. Flow cytometry was used to analyze the immunophenotypes of cells, semi-quantitative RT-PCR and ELISA methods to analyse the mRNA and protein expression levels of interleukin-12 (IL-12). The antigen-presenting function of DCs was determined in one-way mixed leukocyte reaction by Brdu-ELISA technique.

RESULTSThere was a high expression rate (94% approximately 98%) of CD47 molecules in DCs. The cell immunophenotypes in B6H12 mAb treated and untreated DC groups were as follows: CD80(+) (68.14 +/- 7.41)% vs (89.17 +/- 8.59)%; CD86(+) (67.33 +/- 4.71)% vs (87.27 +/- 3.56)%; CD83 (40.08 +/- 14.80)% vs (72.77 +/- 8.68)%; CD1a(+) (66.45 +/- 4.06)% vs (95.93 +/- 3.03)%; and HLA-DR (40.67 +/- 13.48) vs (98.97 +/- 1.01)%, respectively. The expression levels of mRNA and protein of IL-12 were strongly inhibited in B6H12 mAb treated DC (P < 0.01). The quantity of Brdu was also lower in B6H12 mAb treated DC than that in untreated DCs (P < 0.01).

CONCLUSIONThe anti-CD47 McAb exerts a negative effect on the maturation and functions of cultured DCs.

Adult ; Antibodies, Monoclonal ; pharmacology ; Antigens, CD ; analysis ; Antigens, CD1 ; analysis ; B7-2 Antigen ; analysis ; CD47 Antigen ; analysis ; immunology ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dendritic Cells ; cytology ; drug effects ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Humans ; Immunoglobulins ; analysis ; Interleukin-12 ; genetics ; metabolism ; Interleukin-4 ; pharmacology ; Lipopolysaccharides ; pharmacology ; Membrane Glycoproteins ; analysis ; Monocytes ; cytology ; drug effects ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the effects of vascular endothelial growth factor (VEGF) on differentiation and function of dendritic cells derived from CD34+ hematopoietic progenitor cells.

METHODSAfter isolation from umbilical cord blood with a high-gradient magnetic cell sorting system (MACS), the CD34+ cells were cultured with a cocktail cytokines for differentiating into dendritic cells (DC). The cells were stimulated by VEGF (25 ng/ml) either at the beginning or at day 9 of culture. Kinetics analysis of cell proliferation was performed during the process of cell culture, and the expression of DC differentiation antigens including CD1alpha, CD83, CD80, CD54 and HLA-DR was examined by flow cytometry. DC function was evaluated by the ability to induce proliferation of allogeneic T cells in mixed lymphocyte reaction (MLR) assay, and the production of IL-12 by ELISA.

RESULTSVEGF added at day 1 of culture induced an increase of total cell numbers by (1.51 +/- 0.23)-folds (P = 0.001). VEGF added at the initial but not the late stage of culture could dramatically down-regulate the expression of CD1a [(33.00 +/- 2.12)% vs (81.20 +/- 6.93)%], CD83 [(42.23 +/- 1.15)% vs (87.98 +/- 7.97)%], CD80 (42.93 +/- 1.32)% vs (94.53 +/- 0.87)%], and HLA-DR [(37.93 +/- 5.30)% vs (74.15 +/- 3.74)%], while obviously up-regulate the expression of CD14. Moreover, the inhibitory effect of VEGF on DC function was confirmed by a reduced ability to induce proliferation of allogeneic T cells and production of IL-12 (P < 0.01).

CONCLUSIONSVEGF could induce the expansion of hematopoietic progenitor cells and inhibit at the early stage their differentiation into mature DC.

Antigens, CD ; analysis ; Antigens, CD1 ; analysis ; Antigens, CD34 ; analysis ; blood ; B7-1 Antigen ; analysis ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dendritic Cells ; cytology ; immunology ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Fetal Blood ; cytology ; immunology ; Flow Cytometry ; HLA-DR Antigens ; analysis ; Hematopoietic Stem Cells ; cytology ; immunology ; metabolism ; Humans ; Immunoglobulins ; analysis ; Intercellular Adhesion Molecule-1 ; analysis ; Interleukin-12 ; analysis ; Membrane Glycoproteins ; analysis ; Vascular Endothelial Growth Factor A ; pharmacology

The aim was to investigate the cytolytic activity of cytotoxic T lymphocytes (CTL) induced by dendritic cells (DC) derived from human cord blood in vitro. Human cord blood mononuclear cells (CBMNC) were cultured in vitro with addition of various cytokines. DC was confirmed by morphology, immune phenotype and capacity of stimulating MLR (mixed lymphocyte reaction). CTL were generated through the co-culture of autologous T lymphocytes and DC. (51)Cr-release assays were performed for the measurement of cytotoxicity of CTL. The results showed that distribution of the subgroups of T lymphocytes in CBMNC was similar to that in adult peripheral blood. The percentage of CD1a-expressing cells in CBMNC was very low, merely (0.41 +/- 0.09)%. During culture, DC became larger and more irregular in shape. Spiny dendrites or multiple cell processes in morphology emerged on the surface of DC. Among the cell populations at 15 days of culture, there were (28.4 +/- 3.55)% of CD1a-expressing cells, (63.67 +/- 23.33)% of CD86-positive, (8.7 +/- 1.49)% of CD83-positive and (32.5 +/- 1.53)% of HLA-DR-positive cells. DC derived from CBMNC is capable of stimulating the proliferation of allogeneic lymphocytes in MLR. CTL derived from autologous T lymphocytes induced by dendritic cells pulsed with lysates of HL-60 cells, possessed specific cytolytic effects against HL-60 cells. In conclusions, relatively high percentage of CD1a-expressing cells can be generated in culture system of this study. DC derived from cord blood is able to induce the production of anti-leukemic CTL in vitro.
Antigens, CD1 ; analysis ; Cytotoxicity, Immunologic ; Dendritic Cells ; immunology ; Fetal Blood ; immunology ; Humans ; Immunophenotyping ; Leukemia ; immunology ; T-Lymphocytes, Cytotoxic ; immunology