Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The goal of the present paper was to define the immunophenotype of bone marrow mast cells (BMMC) from healthy controls and patients with hematologic malignancies (HM) based on the use of multiple stainings with monoclonal antibodies analyzed by flow cytometry. Our results show that BMMC from both groups of individuals display a similar but heterogeneous immunophenotype. The overall numbers of BMMC are higher in the HM group of individuals (p = 0.08). Three patterns of antigen expression were detected: (1) markers constantly positive in all cases analyzed (CD9, CD29, CD33, CD43, CD44, CD49d, CD49e, CD51, CD71, CD117, and Fc(epsilon)RI), (2) antigens that were constantly negative (CD1a, CD2, CD3, CD5, CD6, CD11a, CD14, CD15, CD16, CD19, CD20, CD21, CD23, CD25, CD30, CD34, CD38, CD41a, CD42b, CD65, CD66b, HLA-DR, and CD138), and (3) markers that were positive in a variable proportion of cases--CD11b (50%), CD11c (77%), CD13 (40%), CD18 (20%), CD22 (68%), CD35 (27%), CD40 (67%), CD54 (88%) and CD61 (40%). In addition, BMMC from all cases explored were CD45+, and this antigen was expressed at an intensity similar to that of mature granulocytes. In summary, our results show that BMMC from both healthy controls and HM patients display a relatively heterogeneous immunophenotype. Interestingly, we have observed clear differences between the immunophenotype of BMMC and MC from other tissues. This could be due either to the heterogeneity of human MC according to their tissue localization or to the sensitivity of the method used for antigen detection.
 ...
PMID:Immunophenotypic characterization of human bone marrow mast cells. A flow cytometric study of normal and pathological bone marrow samples. 969 44

Dendritic cells (DC) are the main stimulators of primary T cell responses. Very little is known about DC in cord blood (CB), and whether they are involved in the low incidence and severity of GVHD following CB transplantation. Here, CBDC were identified as a HLA-DR+/lineage marker (lin; CD3, CD11b, CD14, CD16, CD19, CD34, CD56 and glycophorin A antigens) negative population, representing 0.3 +/- 0.1% (mean +/- s.d.; n = 15) of CB mononuclear cells. CBDC expressed the CD4, CD11a, CD18, CD45RA, CD50 and CD54 antigens but revealed no expression of the CD1a, CD11c, CD40, CD45R0, CD58, CD83, CD86 and CD102 antigens. Immunomagnetically enriched CBDC showed potent allostimulatory activity for CB T cells. Thus, CBDC are functionally competent and resemble in their immature/resting state CD11c- DC in peripheral blood.
 ...
PMID:Functional competence of dendritic cells in human umbilical cord blood. 971 87

After UV exposure of skin, epidermal Langerhans cells (LC) are depleted, whereas CD11b+CD36 CD1a- monocytes/macrophages (UV-Mphi) infiltrate. Different immunological outcomes in vivo are mediated by LC (sensitization) and UV-Mphi (tolerance) which may be related to the distinct T cell activation states that these antigen-presenting cells (APC) induce. We previously demonstrated that CD4+ T lymphocytes activated by UV-Mphi are, in contrast to LC-activated T cells, IL-2Ralpha deficient, and we hypothesize that this differential T cell activation is related to differences in co-stimulatory molecules between UV-Mphi and LC. Using four-color flow cytometry, we found a reduced capacity to up-regulate expression of the important co-stimulatory molecules CD40, B7-1 and B7-2 by UV-Mphi relative to LC. This alteration in co-stimulatory molecule expression was selective, because UV-Mphi express equal levels of ICAM-1 and ICAM-3, and increased levels of LFA-1, relative to LC. After bidirectional signaling with T cells during alloantigen presentation, UV-Mphi still exhibited less CD40 and B7-1 than LC. Addition of IFN-gamma induced CD40 and B7-1 expression on UV-Mphi and restored IL-2Ralpha expression on UV-Mphi-activated T cells but had no effect on IL-2Ralpha on resting or LC-activated T cells. The restoration of IL-2Ralpha expression on UV-Mphi-activated T cells by IFN-gamma was inhibited (67 %, p = 0.005) by addition of neutralizing anti-CD40. Therefore, differences in co-stimulatory molecule expression, in particular CD40, on UV-Mphi and LC are critical in determining the distinct T cell activation induced by these APC.
 ...
PMID:Low expression of CD40 and B7 on macrophages infiltrating UV-exposed human skin; role in IL-2Ralpha-T cell activation. 975 81

Granulocyte macrophage-colony stimulating factor (GM-CSF) is a multipotent cytokine produced by many cutaneous cell types including keratinocytes. Langerhans cells (LC) represent the major antigen-presenting cells in skin, and in vitro studies demonstrate that GM-CSF is of pivotal importance in LC. Healthy volunteers (n = 3 non-atopic, n = 3 with atopy) received recombinant human GM-CSF (0. 05 microg/mL) by intradermal injection for 3 days to the same site. Diluent was injected in a similar manner as control. Biopsies were taken 24 h after the final injection and examined immunohistochemically for LC and inflammatory cell markers. Compared with control sites, intradermal GM-CSF resulted in shortening of dendritic cell processes and redistribution of LC in the epidermis; numbers of CD1a + cells in the epidermis were significantly decreased (P < 0.005), while those in the dermis were significantly increased (P < 0.05) following intradermal GM-CSF when compared with controls. Double labelling studies on epidermal CD1a + cells indicated de novo expression of intercellular adhesion molecule (ICAM)-1 and increased expression of HLA-DR following GM-CSF (P < 0. 005, P < 0.005, respectively). Additional findings included a marked mixed inflammatory cell infiltrate in the dermis and increased expression of the endothelial cell adhesion molecules E-selectin and ICAM-1. These data indicate that in normal human skin, GM-CSF induces changes in the phenotype and distribution of CD1a + cells consistent with LC functional maturation and exit from the epidermis to the dermis. As these events are central to the initiation of cutaneous inflammation, GM-CSF may potentially play a critical role in the pathogenesis of inflammatory dermatoses.
 ...
PMID:Effect of granulocyte macrophage-colony stimulating factor on Langerhans cells in normal and healthy atopic subjects. 976 37

Dendritic cells (DC), the most potent antigen-presenting cells found to date, can be generated from the adherent fraction of peripheral blood mononuclear cells (PBMC) by culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. When interferon gamma (IFN-gamma) was added to the culture medium, the expression of CD1a, CD4 and CD80 markers were significantly reduced, while that of HLA-A, B, C, MHC II (MHC-DR), CD11a and CD54 were increased. T cell proliferation analysis showed that the DC derived from monocytes cultured with GM-CSF, IL-4 and IFN-gamma only induced weak responses in both activated and naive allogenic CD4(+) and CD8(+) T cells when compared to the reaction elicited by DC cultured without IFN-gamma. Furthermore, the DC derived from cultures with IFN-gamma, loaded with an immunogenic peptide derived from the HER2/neu protein [HER2 (9466)], only induced low levels of TNF release and weak proliferative responses in a specific cytotoxic CD8(+) T lymphocyte clone. Therefore, our results indicate that IFN-gamma negatively influences the differentiation and function of monocyte-derived DC by affecting the expression of surface molecules involved in their antigen-presenting function. This supports the general hypothesis that there exists a feedback immune regulatory mechanism between T cells and monocytes/DC.
 ...
PMID:Interferon gamma impairs the ability of monocyte-derived dendritic cells to present tumour-specific and allo-specific antigens and reduces their expression of CD1A, CD80 AND CD4. 981 27

Ultraviolet (UV) irradiation of the skin induces complex local and systemic immunomodulatory reactions. The biological effects of UV irradiation on human skin derived afferent lymph however are unknown. The aim of this study was to examine the effects of a single combined UV-A and UV-B irradiation with 1 minimal erythema dose (MED) on human skin derived lymph in vivo. After cannulation of a superficial lymph vessel on the lower leg, lymph flow and cell output per hour were determined before and for 6 days after UV irradiation of the lymph draining skin area in 5 volunteers. Furthermore, expression of CD1a, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells and cytokine levels (IL-1alpha, IL-1beta, IL-2, IL-6, IL-8, IL-10, IL-13, TNF-alpha and IFN-gamma) in the afferent lymph were analyzed by cytofluorometry and ELISA. After UV irradiation a small initial enhancement in the daily lymph flow per hour was noticed in correlation with the slight erythematous skin reaction. Following resolution of the skin reaction, a delayed increase in cell output in correlation with an additional peak in the lymph flow was found between the 4th and 6th day after UV irradiation. However, no changes in the expression of CD1a, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells were detectable. Interestingly, in parallel to the increased lymph flow and cell output, only elevated IL-8 protein levels were reproducibly detected in the afferent lymph after UV irradiation. Furthermore, using immunohistochemistry positive staining for IL-8 was found on migrating mononuclear lymph cells. In conclusion, our data demonstrate that a single UV irradiation of the skin with 1 minimal erythema dose leads to a delayed enhancement of lymph flow, number of migrating lymph cells and cytokine levels of IL-8. Moreover, we provide evidence that migrating lymph cells, besides resident epidermal and dermal cells, may contribute to the detected levels of IL-8 in the afferent lymph.
 ...
PMID:Effects of UV irradiation with one minimal erythema dose on human afferent skin lymph in vivo. 985 39

Dendritic cells (DC) are the main stimulators of primary T-cell responses and, thus, probably play a role in the immune reactions after stem cell transplantation. Very little is known about DC in cord blood (CB) and about their potential involvement in the low incidence and severity of acute graft-versus-host disease after CB transplantation. Here, CBDC were identified as a HLA-DR+ cell population, lacking the CD3, CD11b, CD14, CD16, CD19, CD34, CD56, and glycophorin A lineage markers (lin). This lin-/HLA-DR+ population represented 0.3% +/- 0.1% (mean +/- SD; range, 0.1% to 0. 6%; n = 15) of CB mononuclear cells, and CB contained 5.4 +/- 3.2 x 10(3) CBDC/mL (1.8 to 13.0 x 10(3); n = 15). CBDC expressed CD4, CD11a, CD18, CD45RA, CD50, CD54, and CD123, but showed no expression of CD1a, CD11c, CD33, CD40, CD45R0, CD80, CD83, and CD86 and only limited expression of CD58, CD102, and CD116. Despite this immature phenotype, immunomagnetically lin--enriched CBDC were potent stimulators of allogeneic CB T cells. As few as 266 +/- 107 (193 to 530; n = 10) lin-/HLA-DR+ CBDC stimulated a significant response. However, CBDC failed to take up protein or peptide antigens. Thus, in CB there is a prevalence of a DC subpopulation, resembling the CD11c- DC identified in tonsils, the so-called plasmacytoid T cells, which may exert a function distinct from the CD11c+ DC subpopulation.
 ...
PMID:Identification of cord blood dendritic cells as an immature CD11c- population. 1009 Sep 40

Because dendritic cells (DC) play a major role in the initiation of T cell-mediated immunity, we studied the effects of glucocorticoids, well-known inhibitors of the immune and inflammatory response, on the differentiation and maturation of human DC. DC were differentiated from human monocytes by culture with GM-CSF and IL-4 for 7 days with and without dexamethasone (Dex). Cells treated with Dex (10-8 M) (Dex-DC) developed a characteristic dendritic morphology; however, membrane phenotype analysis demonstrated that they were not fully differentiated. Dex-DC expressed low levels of CD1a and, unlike untreated cells, high levels of CD14 and CD16. Molecules involved in Ag presentation (CD40, CD86, CD54) were also impaired. In contrast, molecules involved in Ag uptake (mannose receptor, CD32) and cell adhesion (CD11/CD18, CD54) were up-regulated. After exposure to TNF-alpha or CD40 ligand, Dex-DC expressed lower levels of CD83 and CD86 than untreated cells. Dex-DC showed a higher endocytic activity, a lower APC function, and a lower capacity to secrete cytokines than untreated cells. Overall, these results indicate that DC differentiated in the presence of Dex are at a more immature stage. Moreover, Dex also partially blocked terminal maturation of already differentiated DC. In conclusion, our data suggest that glucocorticoids may act at the very first step of the immune response by modulating DC differentiation, maturation, and function.
 ...
PMID:Glucocorticoids affect human dendritic cell differentiation and maturation. 1035 62

Linear IgA bullous dermatosis (LAD) is an acquired, heterogeneous, subepidermal blistering disease characterized by linear IgA deposits at the dermoepidermal basement membrane zone (BMZ), often with circulating IgA antibodies to the BMZ. The pathogenetic mechanism, possibly related to the immunophenotype of infiltrating cells, as well as the potential role of cytokines in determining bullous lesions, have not yet been elucidated. An immunohistochemical study was performed with a large panel of monoclonal antibodies [to CD3, CD4, CD8, CD25, CD1a, CD30, CD54, CD50, endothelial leucocyte adhesion molecule-1, vascular cell adhesion molecule-1, myeloperoxidase (MPO), eosinophil cationic protein EG1 and EG2, tryptase, HLA-DR, human interleukin (IL)-3, human IL-5, human IL-8, human IL-4, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and granulocyte/macrophage colony-stimulating factor] using the alkaline phosphatase-antialkaline phosphatase procedure on lesional and perilesional skin of nine patients (one male, eight female; age range 8 months-80 years) with clinical, histological and immunofluorescent proven LAD. The predominant infiltrating cells, distributed mostly inside and below the bullae, were neutrophils and eosinophils which showed intense activation (MPO +, EG1 +, EG2 +). The lymphocytic infiltrate, consisting principally of CD4 +, HLA-DR + and CD30 + T cells, had a predominantly perivascular distribution. Proinflammatory cytokines, such as TNF-alpha and IFN-gamma, showed a moderate focal expression on the dermal perivascular sites; IL-8 was found to have a particularly intense staining on all the epidermal cell layers and at perivascular and vascular sites. Other cytokines, such as IL-4 and IL-5, showed a prevalent intracytoplasmic staining on some cells of the dermal infiltrate (probably mastocytes and lymphocytes), and at the dermal-epidermal separation sites there was also an intense scattered distribution of IL-5. The specific tissue lesions of LAD may be the consequence of the IgA deposits at the BMZ and also of the release of these cytokines together with tissue damage enzymes derived from neutrophils or eosinophils.
 ...
PMID:The role of lymphocytes, granulocytes, mast cells and their related cytokines in lesional skin of linear IgA bullous dermatosis. 1035 73

High expression of MHC antigens and adhesion/costimulation molecules is considered as one of the major characteristics qualifying macrophages (M) and dendritic cells (DC) as professional antigen presenting cells. Since accessory activity of M is known to be weaker than that of DC but both M or DC can differentiate from blood monocytes (MO) depending on culture conditions (i.e. GM-CSF vs GM-CSF/IL-4), we investigated the kinetics of expression of MHC antigens and several adhesion/costimulation molecules during the differentiation of DC or M from blood MO. Blood MO cultured with GM-CSF consistently induced M that showed adherence to plastic and CD14 expression. In contrast, MO cultured with GM-CSF/IL-4 rapidly became nonadherent, acquired DC morphology and lost CD14 expression. M but not DC proliferated as demonstrated by [H3]thymidine incorporation. MHC Class I was highly expressed in both M and DC. In contrast, MHC Class II molecules were significantly higher on DC compared to M. CD80 was upregulated on both DC and M but only on a subset of cells. CD80 expression peaked at day 3 on M and declined thereafter, while on DC expression increased significantly until day 10. CD86 was upregulated on the majority of DC and M. However, while M maintained stable expression of CD86 after day 3, DC progressively upregulated CD86 throughout the culture period. CD1a expression was initially low in both cell types and peaked at day 3 in M declining thereafter, while expression remained stable on DC until day 10. ICAM-1 expression was significantly upregulated on M when compared to DC at day 3. However, on M, ICAM-1 expression became undetectable by day 5 while on DC it increased through day 10. Similarly, CD40 was transiently expressed on M until day 5, while on DC it continuously increased until day 10. Finally, in contrast to other antigens, LFA-3 was always more strongly expressed on M than DC at all culture periods. Taken together, these data suggest that M showed a rapid but transient upregulation in the expression of adhesion/costimulation molecules, suggesting that maximal accessory ability is reached by M at an earlier time point than DC. Significant differences in surface antigen expression DC vs M were recognizable for MHC class II, CD86, CD80, CD1a, CD40 and ICAM-1. Specifically, major differences occurred for MHC class II, CD86, CD40 and ICAM-1. Therefore, the higher accessory ability of DC compared to M in naive T cell priming may be related to qualitative and quantitative differences in expression of these immunologically important surface molecules.
 ...
PMID:Expression of surface antigens during the differentiation of human dendritic cells vs macrophages from blood monocytes in vitro. 1041 27


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>