OBJECTIVETo investigate the expressions of CD1a and CD83 of Langerhans cells (LC) in the lesions of epidermodysplasia verruciformis (EV) patients.

METHODSWe used immunohistochemical method to detect the expressions of CD1a and CD83 in the lesions of 10 patients with EV lesions and in the skins of 10 normal subjects.

RESULTSNo CD83 + LCs was detected in all EV patients and normal controls, but CD1a + LC was found in all cases. The quantity of CD1a + LCs in the lesions of EV patients was significantly lower than that in the normal skin (P < 0.01); furthermore, the distribution of LCs in EV lesions was uneven.

CONCLUSIONThe functions of LCs may be inhibited in EV patients.

Antigens, CD ; biosynthesis ; genetics ; Antigens, CD1 ; biosynthesis ; genetics ; Epidermodysplasia Verruciformis ; immunology ; pathology ; Humans ; Langerhans Cells ; immunology ; Leukocyte Immunoglobulin-like Receptor B1 ; Receptors, Immunologic ; biosynthesis ; genetics ; Skin ; immunology ; pathology

Langerhans cell sarcoma (LCS) is a neoplastic proliferation of Langerhans cells that have overtly malignant cytologic features. It is a very rare disease and theoretically, it can present de novo or progress from an antecedent Langerhans cell histiocytosis (LCH). However, to our knowledge, LCS arising from an antecedent LCH has not been reported on. We present here a case of LCS arising from a pulmonary LCH. A 34 yr-old man who was a smoker, had a fever and a chronic cough. Computed tomographic (CT) scan revealed multiple tiny nodules in both lungs. The thoracoscopic lung biopsy revealed LCH. The patient quit smoking, but he received no other specific treatment. One year later, the follow up chest CT scan showed a 4 cm-sized mass in the left lower lobe of the lung. A lobectomy was then performed. Microscopic examination of the mass revealed an infiltrative proliferation of large cells that had malignant cytologic features. Immunohistochemical stains showed a strong reactivity for S-100 and CD68, and a focal reactivity for CD1a. We think this is the first case of LCS arising from LCH.
Tomography, X-Ray Computed ; Sarcoma/*pathology ; S100 Proteins/biosynthesis ; Radiography, Thoracic ; Pancreatic Neoplasms/*pathology ; Male ; Langerhans Cells/*pathology ; Immunohistochemistry ; Humans ; Histiocytosis, Langerhans-Cell/diagnosis/*pathology ; Gene Expression Regulation, Neoplastic ; Antigens, Differentiation, Myelomonocytic/biosynthesis ; Antigens, CD1/biosynthesis ; Antigens, CD/biosynthesis ; Adult

To investigate the influence and mechanisms of CD47 engagement by its soluble mAb B6H12 on the maturation and function of cultured dendritic cells (DCs), monocyte-derived DCs were propagated in granulocyte-macrophage colony stimulating factor (GM-CSF) combined with lipopolysaccharide (LPS) and interleukin (IL)-4, in the presence or absence of soluble anti-CD47 monoclonal antibodies (anti-CD47 mAbs, B6H12). The characteristic morphology of DCs was identified by using the transmission electron microscopy. Flow cytometry was used to detect the cell surface phenotypes. The concentration of IL-12 P70 in supernatant was measured by ELISA. The antigen-presenting functions of DCs were determined in one-way mixed leukocyte reaction by BrdU-ELISA. Electrophoretic mobility shift assay (EMSA) was applied to examine the activity of NF-kappaB. The results indicated that the anti-CD47 mAbs markedly suppressed the expression of CD80, CD86, CD83, CD1a and HLA-DR on the surface of DCs (P < 0.05). The data of the mixed leukocyte reaction and IL-12 P70 production were consistent with the results by flow cytometry (P < 0.01). Pre-exposure to B6H12 mAb during the development of DCs resulted in a dramatic depletion of the DNA binding activity of NF-kappaB toward nucleus protein. Moreover, such an inhibition effect seemed to be dose dependent. In conclusion, the soluble mAb B6H12 inhibits the expression of the costimulatory molecules and MHCII molecules on the DCs. The antigen-presenting function of DCs was also impaired by B6H12. And these modulations are closely related with the depletive DNA binding activity of NF-kappaB. It is suggested that the soluble B6H12 exerts a negative effect on the maturation and function of in vitro cultured DCs due to inhibition of NF-kappaB binding activity.
Antibodies, Monoclonal ; immunology ; pharmacology ; Antigens, CD ; biosynthesis ; Antigens, CD1 ; biosynthesis ; B7-1 Antigen ; biosynthesis ; B7-2 Antigen ; biosynthesis ; CD47 Antigen ; immunology ; Cell Size ; drug effects ; Cells, Cultured ; Dendritic Cells ; cytology ; drug effects ; metabolism ; Electrophoretic Mobility Shift Assay ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; HLA-DR Antigens ; biosynthesis ; Humans ; Immunoglobulins ; biosynthesis ; Interleukin-12 ; metabolism ; Membrane Glycoproteins ; biosynthesis ; NF-kappa B ; metabolism ; Oligonucleotides ; metabolism ; Protein Binding

OBJECTIVE: To investigate the tumor-suppression effect of PA combined with GM-CSF, TNF-alpha and IL-4 on cord blood mononuclear cells (CBMC). METHODS: The mononuclear cells were isolated from human umbilical cord blood and cultured with polyacttin A (PA), GM-CSF + TNF-alpha + IL-4 (GTI), and GTI + PA (GTIP) respectively. Six days later, surface antigen expression of the cultured cells, including CD1a and CD83, which were the specialized markers of dendritic cell (DC), were analyzed by immunohistochemistry technique. The CBMC were cultured with GTI for 24 h to enhance DC, then were added apoptotic/necrotic Hela/HepG2 tumor cells, and finally PA was co-cultured. The antitumor cytotoxicity of CBMC was measured by MTT assay. RESULTS: After the culture, CD1a and CD83 positive cell rates of the PA group inreased significantly, reaching (19.63 +/- 3.61)%, (9.28 +/- 4.31) % respectively, much higher than that of the control, but lower than that of the GTI group. The killing rate to the tumor cells of CBMC cultured with GTIP increased remarkably, much higher than the control, GTI and PA groups. After tumor antigens were added to the CBMC of GTIP group (GTIP + Tc), the killing rate increased. CONCLUSION PA not only promotes the proliferation and maturation of cord blood derived DC, but also improves the tumor-suppression effect of CBMC cultured with GTI.
Antigens, CD ; biosynthesis ; genetics ; Antigens, CD1 ; biosynthesis ; genetics ; Cells, Cultured ; Fetal Blood ; cytology ; Glycopeptides ; pharmacology ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; HeLa Cells ; Humans ; Immunoglobulins ; biosynthesis ; genetics ; Immunotherapy ; Interleukin-4 ; pharmacology ; Leukocytes, Mononuclear ; drug effects ; immunology ; Liver Neoplasms ; pathology ; therapy ; Membrane Glycoproteins ; biosynthesis ; genetics ; Neoplasms ; therapy ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha ; pharmacology

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

Staphylococcus aureus may perform an crucial function in atopic dermatitis (AD), via the secretion of superantigens, including staphylococcal enterotoxins (SE) A or B, and toxic shock syndrome toxin-1 (TSST-1). Dysregulated cytokine production by keratinocytes (KCs) upon exposure to staphylococcal superantigens (SsAgs) may be principally involved in the pathophysiology of AD. We hypothesized that lesional KCs from AD may react differently to SsAgs compared to nonlesional skin or normal skin from nonatopics. We conducted a comparison of HLA-DR or CD1a expression in lesional skin as opposed to that in nonlesional or normal skin by immunohistochemistry (IHC). We also compared, using ELISA, the levels of IL-1alpha, IL-1beta, and TNF-alpha secreted by cultured KCs from lesional, nonlesional, and normal skin, after the addition of SEA, SEB and TSST-1. IHC revealed that both HLA-DR and CD1a expression increased significantly in the epidermis of lesional skin versus nonlesional or normal skin in quite a similar manner. IL-1alpha, IL-1beta, and TNF-alpha secretion was also significantly elevated in the cultured KCs from lesional skin after the addition of SsAgs. Our results indicated that KCs from lesional skin appear to react differently to SsAgs and increased proinflammatory cytokine production in response to SsAgs may contribute to the pathogenesis of AD.
Tumor Necrosis Factor-alpha/biosynthesis/genetics ; *Superantigens/administration & dosage/immunology ; Staphylococcus aureus/*immunology/pathogenicity ; Male ; Keratinocytes/immunology/*microbiology ; Interleukin-1/biosynthesis/genetics ; Inflammation Mediators/metabolism ; Humans ; HLA-DR Antigens/metabolism ; Enterotoxins/administration & dosage/immunology ; Dermatitis, Atopic/etiology/immunology/*microbiology ; DNA, Complementary/genetics ; Case-Control Studies ; Base Sequence ; Bacterial Toxins/administration & dosage/immunology ; Antigens, CD1/metabolism ; Adult

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