Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UNIPROT:P06126 (CD1a)
2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have shown that gamma delta T cells in human gingiva have an intraepithelial location and, that in the chronic inflammatory disease periodontitis, the expression of CD45RO and CD8 or CD4 is induced on gamma delta T cells. To study the role of gamma delta T cells in local antibacterial responses, we determined the cytokine profiles of isolated human gingival cells. Different T cell subpopulations, isolated by positive selection with mAb-coated magnetic beads and macrophages, as well as epithelial cells, were analyzed for expression of mRNA for 15 cytokines by reverse transcriptase-PCR. The ultrastructure of gingival gamma delta T cells was also studied. The gamma delta T cells expressed mRNA for IFN-gamma, TNF-alpha, TGF-beta 1, and IL-6. Expression of IFN-gamma was a consequence of inflammation. CD4+ gamma delta T cells expressed IFN-gamma only, whereas CD8+ gamma delta T cells expressed all four cytokines. CD8+ cells expressing IFN-gamma, TNF-alpha, and IL-6 in combination suggest a cytotoxic effector function. Gingival gamma delta T cells contained cytoplasmic electron-dense membrane-bound granules and multivesicular bodies that are ultrastructural characteristics of cytotoxic cells. Epithelial cells from inflamed gingiva expressed HLA-DR, CD1a, CD1c, and heat shock protein 60 on the cell surface. They also expressed mRNA for IL-1 beta, IL-6, IL-8, TNF-alpha, and TGF-beta 1. Thus, epithelial cells may function as accessory cells in immune activation and, at the same time, be target cells for CD8+ gamma delta T cells reactive with CD1 Ag or heat shock protein. These results suggest that gamma delta T cells constitute a first line of defense in gingiva, preventing entrance of pathogens by cytotoxicity against infected and stressed epithelial cells, and by control of epithelial cell growth through secretion of regulatory cytokines.
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PMID:Cytokine profile and ultrastructure of intraepithelial gamma delta T cells in chronically inflamed human gingiva suggest a cytotoxic effector function. 805 26

We postulate that wound healing is an orderly process mediated by a programmed expression of cytokines and growth factors. We suggest that these factors are produced in a consistent sequence, in regulated quantities and eliminated when their function is complete. We report here the results of studies on several cytokines, growth factors and the intercellular adhesion molecule expressed during the healing of grafts were visible clinically around 3-5 days post-graft and were completed by 4 weeks post-graft. During the 1st 2 weeks, we observed the following. (i) K-14 keratin was prominent throughout the entire epidermis. Thereafter it was limited to basal cell layers. (ii) Langerhans cells were not detectable with anti-human CD1a antibodies during the first week of healing but were clearly detectable 2 weeks post-graft. (iii) DOPA (dihydroxy phenylalanine) positive melanocytes gradually increased with time. The epidermis 21 to 28 days post-graft clinically and histologically seemed to be morphologically intact. Interleukin-1 (IL-1) was clearly detected in some basal cells of the epidermis, especially in melanocytes and some keratinocytes during the early stage of healing. Transforming growth factor-alpha (TGF-alpha) was detected in epidermis first in melanocytes and some keratinocytes shortly after grafting and again in the late stage of healing. It was also found in some dermal cells. Its expression coincided with keratinocyte proliferation and melanocyte migration. TGF-beta was strongly expressed in the epidermis and dermis after the first week post graft. (iv) ICAM-1 was transiently expressed only at the onset of healing. We previously reported that pro-opiomelanocortin and its derivatives MSH/ ACTH are expressed strongly during the healing of human xenografts. The 4 additional molecules which are the subject of this report all are expressed in healing human skin in a predictable sequence and quantity (intensity of stain). Together these data support our hypothesis that healing is a highly regulated process mediated by numerous cytokines.
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PMID:The expression of cytokines, growth factors and ICAM-1 in the healing of human cutaneous xenografts on nude mice. 906 2

Dermatofibroma is composed largely of interlacing fascicles of slender spindle cells set within a loose collagenous stroma and of scattered foamy histiocytes and multinucleated giant cells. There is clear evidence indicating that factor XIIIa+ dermal dendritic cells (DDCs) are the cells constituting dermatofibromas. However, it is still unknown what stimulation is responsible for transforming DDCs into different cell types, producing different subtypes of dermatofibromas. Recently, it has become possible to obtain dendritic cells (DCs), that are identical with DDCs in their phenotypic and functional characteristics, from the culture of CD14+ peripheral blood monocytes to which IL-4 and GM-CSF were added. Using these monocyte-derived DCs, we examined the ability of various cytokines, such as IL-1beta , IL-3, IL-5, IL-6, IL-7, IL-8, IL-10, TNFalpha, TGFbeta, M-CSF, IFNalpha, and IFNgamma, and phorbol 12-myristate 13-acetate (PMA), to induce different cell types observed in DFs. Among them, only PMA could induce a variety of cell types such as histiocytic cells, fibroblastic spindle-shaped cells, and even multinucleated giant cells of Touton or foreign body type. Phenotypically, all the induced cell types expressed CD1a, CD80, CD86, HLA-DR, and CD68 in a magnitude similar to that of non-treated monocyte-derived DCs. The expression of factor XIIIa was strongest in histiocytic cells, moderate in fibroblastic cells, and weakest or negative in giant cells. These data suggest that dermatofibromas are a kind of neoplastic disease which is induced only by the effect of some tumor promoter on DDCs.
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PMID:Phorbol 12-myristate 13-acetate can transform monocyte-derived dendritic cells to different cell types similar to those found in dermatofibroma. A possible in vitro model of the histogenesis of dermatofibroma. 952 94

We examined the effects of different cytokine combinations and culture conditions on the expansion and modulation of cell surface antigens of CD34+ derived dendritic cells (DCs), the most efficient antigen-presenting cells capable of stimulating resting T cells in the primary immune response. Cells with a dendritic morphology and expressing HLA-DR, CD1a, S100 and CD83 were maximally expanded under serum-free conditions with the addition of SCF, GM-CSF, TNF-alpha, TGF-beta and Flt-3 ligand (fold increase of CD1a+ cells = 102 +/- 32 after 2 weeks of culture). CD34+ cells were also grown under continuous flow conditions in an artificial capillary system: after 14d of culture, the expansion in the total cell number was lower than that of the static cultures (3.3 +/- 2 v 18.9 +/- 4) but the percentage of CD1a+/CD83+/ CD80+ cells was considerably higher, whereas the CD14+ cells were significantly reduced (8.9 +/- 2 v 26 +/- 13). In continuous perfusion cultures, low levels of DC precursors and of LTC-IC were still present up to day 14. The DCs generated under flow conditions stimulated the mixed leucocyte reaction (MLR) more than the cells grown in static cultures. By electron microscopy, cells grown in the continuous flow system showed an increased number of large cells with numerous dendritic processes and abundant multilamellar complexes. The cells expanded under these conditions were sorted on the basis of their light-scatter properties into two fractions: one containing a predominance of CD1a+/S100+/ CD8 3+/CD80+/CD14- 'large cells' with great internal complexity (mature DCs); the second including 'small cells' either CD33+/CD14+, CD33+/CD15+ or CD33+/CD13-/CD14. The DCs generated and selected with this method are therefore particularly well suited for immunotherapeutic protocols.
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PMID:Expansion of dendritic cells derived from human CD34+ cells in static and continuous perfusion cultures. 960 35

Dendritic cells (DCs) are the most efficient antigen presenting cells (APCs) that initiate and modulate our internal immune responses in stimulating both B cells to produce various antibodies and T cells to control cell-mediated immunity. Such DCs can be classified into three groups based on their origin. One is the myeloid DCs originating from CD34+ stem cells that are further differentiated into CD14+ CD1a- phagocytotic, glass-adherent macrophages with the help of M-CSF, or into CD14- CD1a+, Birbeck granule containing LAG-1+ Langerhans cells by GM-CSF, TNF-alpha and TGF-beta 1 stimulation. The latter Langerhans cells appear to differentiate into DC1 as strong stimulators of T cells displaying large amounts of MHC-peptide complexes and co-stimulatory molecules, such as B7-1 and B7-2, after capturing antigens and migrating to a regional lymphoid organ. The second group is the lymphoid DCs originating from CD4+CD11c- cells, which differentiate into DC2 when cultured with IL-3. Third is the follicular dendritic cells (FDC) observed in lymphofollicules that capture foreign antigens with their Fc-receptor or complement-receptors and keep the antigens inside the follicules. DC1s secrete IL-12, which turns CD4 T cells into Th1 cells to induce cellular immunity, whereas DC2s favor production of Th2 cells to organize humoral immunity. Therefore, DCs appear to control our internal self-defense system. These unique features of DCs enable us to manipulate Th1 and Th2 activation selectively, and thus antigen-pulsed DCs are currently thought of as excellent tools to induce specific T cell immunity towards virus-infected cells or tumor cells.
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PMID:[Dendritic cells and tumor specific immunity]. 1063 93

Epithelial Langerhans cells (LC) represent immature dendritic cells that require TGF-beta 1 stimulation for their development. Little is known about the mechanisms regulating LC generation from their precursor cells. We demonstrate here that LC development from human CD34+ hemopoietic progenitor cells in response to TGF-beta 1 costimulation (basic cytokine combination GM-CSF plus TNF-alpha, stem cell factor, and Flt3 ligand) is associated with pronounced cell cluster formation of developing LC precursor cells. This cell-clustering phenomenon requires hemopoietic progenitor cell differentiation, since it is first seen on day 4 after culture initiation of CD34+ cells. Cell cluster formation morphologically indicates progenitor cell development along the LC pathway, because parallel cultures set up in the absence of exogenous TGF-beta 1 fail to form cell clusters and predominantly give rise to monocyte, but not LC, development (CD1a-, lysozyme+, CD14+). TGF-beta 1 costimulation of CD34+ cells induces neoexpression of the homophilic adhesion molecule E-cadherin in the absence of the E-cadherin heteroligand CD103. Addition of anti-E-cadherin mAb or mAbs to any of the constitutively expressed adhesion molecule (CD99, CD31, LFA-1, or CD18) to TGF-beta 1-supplemented progenitor cell cultures inhibits LC precursor cell cluster formation, and this effect is, with the exception of anti-E-cadherin mAb, associated with inhibition of LC generation. Addition of anti-E-cadherin mAb to the culture allows cell cluster-independent generation of LC from CD34+ cells. Thus, functional E-cadherin expression and homotypic cell cluster formation represent a regular response of LC precursor cells to TGF-beta 1 stimulation, and cytoadhesive interactions may modulate LC differentiation from hemopoietic progenitor cells.
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PMID:Functional involvement of E-cadherin in TGF-beta 1-induced cell cluster formation of in vitro developing human Langerhans-type dendritic cells. 1090 41

The dermis harbors a true dendritic cell population that could elicit primary allogeneic T cell responses in vitro and contact hypersensitivity reactions in vivo. The origin of dermal dendritic cells remains poorly understood, however. In this study, we analyzed the fate of monocytes or monocyte-derived dendritic cells in a dermal equivalent. Freshly isolated monocytes or monocytes cultured for 6 d with either GM-CSF/IL-4 or GM-CSF/IL-4/TGF-beta 1 (TGF-DC) were seeded in a collagen solution with normal human fibroblasts. The lattices were cultured for 7--14 d in the presence, or absence, of the exogenous cytokines, before phenotypic and functional studies were performed. Supply of exogenous cytokines allows the appearance of typical CD1a(+)/CD14(-)/CD68(low) dendritic cells with significant allostimulatory property, regardless of the cell type incorporated into the lattices. In cytokine-free conditions, monocytes and GM-CSF/IL-4-derived dendritic cells give rise to a CD1a(-)/CD14(+)/CD68(high) monocyte/macrophage population with no allostimulatory property. When incorporated into the lattices in the absence of exogenous cytokines the TGF-DC express few CD68 and FXIIIa. Interestingly, these cells do not all convert into the CD14(+)/CD1a(-) population. Indeed, a small HLA-DR(+)/CD1a(+)/CD14(-) subset was consistently found, which represents about one-third of the HLA-DR(+) cells. Moreover, TGF-DC recovered from the lattices after culture without cytokines do display a significant allostimulatory function. Thus, in the absence of exogenous cytokines, only Langerhans-cell-like dendritic cells can retain the typical dendritic cell features when inserted in a dermal environment. Taken together, these results may provide evidence supporting an epidermal origin of dermal dendritic cells.
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PMID:Phenotypic and functional outcome of human monocytes or monocyte-derived dendritic cells in a dermal equivalent. 1140 84

Tumour-derived factors suppress differentiation and function of in vitro generated DC. Here, we investigate the effect of two melanoma clones differing in their invasive and metastatic properties on the generation and/or functional maturation of human epidermal LC. LC were generated from CD34(+) cord blood progenitors under GM-CSF/TNF-alpha/TGF-beta 1. CD34(+) cells were co-cultured with or without melanoma cells using Transwell dishes. After 11 days of co-culture, CD34(+)-derived cells display a non-adherent undifferentiated morphology, a high level of monocytic CD14 marker, a down-regulated expression of LC markers (CD1a, E-cadherin) and DC markers (CD40, CD80, CD54, CD58, CD83, CD86, HLA-DR, HLA-class I). These cells were less potent than control LC in inducing allogeneic T cell proliferation. The generation of the CD14(+) population was correlated with a decrease in the CD1a(+) population, without any statistical differences between the two clones. Melanoma cells diverted the differentiation of CD34(+) cells towards a dominant CD14(+) population only if the progenitors were in an early growth phase. IL-10, TGF-beta 1 and VEGF were not responsible for these effects, as assessed by using blocking antibodies. By contrast, co-culture of fresh epidermal LC with melanoma cells did not affect their phenotype and function. Our data demonstrate that melanoma cells inhibit the earliest steps of LC differentiation, but failed to affect the functional maturation of epidermal LC. This suggests that melanoma cells participate in their own escape from immunosurveillance by preventing LC generation in the local cutaneous microenvironment.
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PMID:Human melanoma cells inhibit the earliest differentiation steps of human Langerhans cell precursors but failed to affect the functional maturation of epidermal Langerhans cells. 1174 38

The American cutaneous forms of leishmaniasis include immune-responder individuals with localised cutaneous leishmaniasis (LCL) and non-responder individuals with diffuse cutaneous leishmaniasis (DCL). Patients with intermediate or chronic cutaneous leishmaniasis (ICL) have increased morbidity due to the length of their illness, atypical forms and areas of compromise. In the present study, we evaluated the expression of the leukocyte antigens (CD4, CD8, CLA: cutaneous lymphocyte antigen, CD69, CD83 and CD1a) and cytokines (IFN-gamma, IL-4, IL-10 and TGF-beta 1) in the lesions of patients with ICL (n = 18) using an immunocytochemical procedure. ICL results were compared with the information for LCL (n = 19) and DCL (n = 4). The numbers of CD4+ and CD8+ T cells in ICL were similar to those of LCL lesions, but significantly different (P < or = 0.05) from DCL lesions. LCL lesions have about half the numbers of early activated CD69+ cells as ICL, but most are CLA+ skin homing memory T cells, whereas ICL lesions have the highest number of CD69+ T cells, but about one-third of these cells expressed CLA. This suggests that the granuloma of ICL patients contains many activated T cells that are unprimed to cutaneous-launched antigens, thus contributing to an aberrant immune response. In contrast, DCL granulomas presented the lowest numbers of activated CD69+ and CLA+ cells, associated with the characteristic tolerogenic state of these patients. The immunolocalisation of cytokines showed a mixed cytokine pattern in ICL lesions with many positive cells for IL-10, TGF-beta 1, IL-4 and IFN-gamma, with a preponderance of the first two, and different from the prevalent Th1 and Th2 responses associated with LCL and DCL lesions, respectively. CD1a+ Langerhans cells were decreased (P < or = 0.05) in both ICL (271 +/- 15 cells/mm2) and DCL (245 +/- 19 cells/mm2) as compared to LCL (527 +/- 54 cells/mm2) epidermis. The percentage of IL-10+ epidermal Langerhans cells in ICL (33.69), from the total CD1a+ population, was higher than in LCL (17.45). In addition, fewer CD83+ primed Langerhans cells were present in ICL epidermis. The diminished participation of epidermal Langerhans cells, causing a defective signalling by the epidermis, in ICL lesions may account for the tissue-damaging state observed in these patients.
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PMID:Intermediate or chronic cutaneous leishmaniasis: leukocyte immunophenotypes and cytokine characterisation of the lesion. 1195 26

BACKGROUND The pathogenesis of Langerhans cell histiocytosis (LCH), a disease characterized by an abnormal accumulation of the dendritic Langerhans cells, is still unknown. Based on the monoclonality of the CD1a+ cell and reports of familial clustering, it is hypothesized that a genetic alteration at a cellular level may be causative. This genetic change may have an effect on the cellular mechanisms controlling proliferation and apoptosis. MATERIALS AND METHODS LCH-lesions were studied for the expression of Ki-67, present in the nucleus of proliferating cells. Furthermore, the expression of cell cycle-related gene products TGF-beta receptor I and II, MDM2, p53, p21, p16, Rb, and Bcl2 were studied. The TGF-betaR genes play a role in tumor suppression, whereas Bcl2 inhibits apoptosis. The remaining genes are part of either the p53-p21 and/or p16-Rb pathways, which induce cell cycle arrest or apoptosis in response to DNA damage. RESULTS In 30 biopsies the diagnosis of LCH could be confirmed on the basis of CD1a positivity (27 bone and 3 skin). All cases showed scattered nuclear-positive staining for the proliferation marker Ki-67. In more than 90% (n >/=27) of these cases, expression of TGFbeta receptor I and II, MDM2, p53, p21, p16, Rb, and Bcl2 was detected in lesional LCH cells. The overexpression was in general heterogeneous, ranging from limited focal staining of scattered cells within the lesion to strong diffuse staining. CONCLUSIONS These findings suggest that the cellular mechanisms that sense and respond to DNA-damage, namely the p53-p21 pathway and the p16-Rb pathway, are activated. The expression of Ki-67 indicates that the cells in LCH are proliferating. The observed overexpression of Bcl2 may play a role in the activation of p53 and p16 and/or the arrest of apoptosis.
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PMID:Expression of cell cycle-related gene products in Langerhans cell histiocytosis. 1246 13


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