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 developed a method for isolating and characterizing pigtailed macaque dendritic cells (DCs) generated from CD34(+) bone marrow (BM) progenitors based on methods previously developed for isolating human DCs. Macaque DCs displayed a characteristic morphology and were potent stimulators of allogeneic T cell proliferation. They expressed a set of DC-associated markers, such as MHC class II, CD1a, CD4, CD11a, CD40, CD58, CD80, CD83, CD86, and CXCR4. Macaque DCs, as well as peripheral blood CD4(+) T cells, were highly susceptible to HIV-2 infection, as detected by DNA-PCR. The expression of HIV-2 in macaque DCs was downregulated by treatment with the beta-chemokine RANTES. Macaque DCs will be useful for defining the in vivo role of DCs in HIV pathogenesis and for optimizing and testing peptide-DC vaccines or tolerizing regimens.
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PMID:Isolation and characterization of macaque dendritic cells from CD34(+) bone marrow progenitors. 1048 53

Vasculitic neuropathy and chronic inflammatory demyelinating polyneuropathy (CIDP) are neuropathies characterized by a T-lymphocyte infiltrate in the peripheral nerves. The microenvironment in which these T cells become activated, and the molecules and cells that play a role in this process are incompletely understood. Using immunohistochemical analysis, we studied the effect of the presence of adhesion, costimulatory and antigen-presenting molecules on different cell types as a precondition for local T-cell activation in human sural nerve biopsies of seven patients with CIDP, three patients with vasculitic neuropathy and three healthy controls. In biopsies from CIDP and vasculitic neuropathy patients, but not in those from healthy controls, Schwann cells expressed the adhesion/T-cell stimulatory molecule CD58 (LFA-3). The CD58 molecule was also present on endothelial cells of all vasculitic neuropathy patients and one CIDP patient. In biopsies from normal controls and patients, CD54 (ICAM-1) expression was detectable on microvascular endothelial cells. In addition, expression of the costimulatory molecule CD86 was detected on vascular tissue in patients with vasculitic neuropathy. Although macrophages were always present in all subjects, expression of the major histocompatibility complex (MHC)-like molecule CD1a by macrophages was restricted to biopsies from two CIDP patients and one vasculitic neuropathy patient. Unexpectedly, Schwann cells of a single vasculitis patient strongly expressed CD1b, a molecule involved in the presentation of self-glycolipids to T cells. Schwann cells in biopsies from patients and normal controls expressed high levels of the invariant chain, CD74, a molecule involved in the intracellular sorting of MHC class II molecules. There was no evidence for the presence of dendritic cells in sural nerve biopsies. These findings support a model in which T-cell activation can be initiated and/or perpetuated locally in sural nerve biopsies of patients with CIDP and vasculitic neuropathy, and predict an important role for Schwann cells and endothelial cells.
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PMID:Expression of accessory molecules for T-cell activation in peripheral nerve of patients with CIDP and vasculitic neuropathy. 1100 19

Presentation of cell-associated antigen to T cells is a critical event in the initiation of an anti-tumor immune response but it appears to often be deficient or limiting. Here we report an experimental system for stimulation of human T lymphocytes using autologous antigen presenting cells (APCs) and autologous tumor cells. Two types of APCs were prepared from human bone marrow: MC and DC. MC were produced by using GM-CSF and SCF. DC were obtained with the same cytokines plus IL-4. DC and MC were generated in parallel from the same patients and their phenotypes and capacities to prime T lymphocytes were analyzed and compared. MC were CD14+, CD1a-, CD33+ and HLA-DR+. Two populations of DC were defined: immature DC were uniformly CD1a-; mature DC expressed CD1a, CD80, CD86, HLA-DR, CD54 and CD58 but lacked surface CD14. Stimulation of autologous T lymphocytes was studied by measuring their proliferation and cytotoxic function. In more than 80% of our experiments the proliferation of autologous T lymphocytes cocultured with APC pulsed or not with tumor cell lysates was higher than that of T cells cultured alone. DC were more effective than MC in stimulating proliferation of lymphocytes. The capacity of a patient's autologous bone marrow-derived APC to stimulate T cells when exposed to autologous tumor cell lysates suggest that such antigen-exposed APC may be useful in specific anti-tumor immunotherapy protocols.
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PMID:In vitro immunization of patient T cells with autologous bone marrow antigen presenting cells pulsed with tumor lysates. 1107 49

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 object of this study is to explore a culture method to generate a large number of functional and mature dendritic cells (DC) from human CD34+ hematopoietic progenitor cells. In the present study, we used a two-step method combined with calcium ionophore to induce DC from cord blood (CB) or normal human bone marrow (BM) CD34+ progenitor cells. The two-step method consists of 10 days of first step culture for the expansion and proliferation of CD34+ hematopoietic progenitor cells in the presence of SCF, IL-3, IL-6, G-CSF, and 7--11 days of second step culture for the induction of DC in the presence of GM-CSF, IL-4 and TNF-alpha. By the two-step culture, total nucleated cells were increased 208+/-66 (+/-SD, n=13), or 94+/-29 (n=5)-fold in the culture of CB or BM cells, respectively, compared with the number of CD34+ cells at the time of starting culture. Out of the total nucleated cells, 23 +/-10.4% of cells in CB cell culture and 25 +/-5% of cells in the BM cell culture acquired DC characteristic phenotypes, which were marked expressions of CD1a, HLA-DR, co-stimulatory molecules such as CD80, CD40, and adhesion molecule such as CD58. In allogeneic mixed leukocyte reaction (MLR), two-step cultured cells showed potent allo-stimulatory capacity. With this two-step culture, the absolute number of CD1a+ cells that co-expressed HLA-DR, CD80, CD40 and CD58 was enhanced approximately 3 times in CB cell culture and 1.9 times in BM cell culture, compared with the commonly used one-step culture method for the generation of DC from CD34+ cells using SCF, GM-CSF and TNF-alpha. However, on these DC generated in the two-step culture, the expressions of co-stimulatory molecule CD86 and mature DC marker CD83 were not sufficient. By the treatment of two-step cultured cells with calcium ionophore agent (A23187), the expression of co-stimulatory molecules such as CD86 and CD80 (especially CD86) was up-regulated. Besides, the expression of mature DC marker CD83 was remarkably induced by treatment with A23187 for a short duration (24 h). Consistent with the up-regulation of surface molecules CD86, CD80 and CD83, the two-step cultured cells treated with A23187 also showed a stronger allo-stimulatory capacity compared with the cells without A23187 treatment. In conclusion, the present study demonstrated that the two-step culture method effectively improved the yield of CD1a+ DC generated from CD34+ cells, and the phenotypes and functions of these CD1a+ DC could be enhanced efficiently by treatment with a calcium ionophore agent.
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PMID:Generation of functional and mature dendritic cells from cord blood and bone marrow CD34+ cells by two-step culture combined with calcium ionophore treatment. 1186 Oct 65

Dendritic cells are professional antigen presenting cells which are being used as adjuvants in tumor vaccination trials. Most clinical protocols currently include 4 to 10 weekly infusions of doses > 10(6) cells, each inoculum coming from a simple culture of blood monocytes. In the present study, several millions of dendritic cells from a single leukapheresis were produced; monocytes were isolated by elutriation and then cultured in Teflon bags in presence of 800 U/ml GM-CSF + 100 micro g/ml IL-13 + 10% fetal calf serum (FCS). The dendritic cells from this single batch were aliquoted in many doses for potential multiple infusions and cryopreserved in 10% DMSO + 2% human albumin in Teflon-kapton Fresenius bags either at -1 degrees C/min using a controlled rate freezer, or putting the bags directly in a -80 degrees C mechanical freezer without controlling the temperature rate. Six experiments were carried out. After one month of cryopreservation, the cells were thawed in a 40 degrees C water bath. Before and after freezing, cells were evaluated for immunophenotype (CD1a, CD14, CD40, CD80, CD83, CD86, CD54, CD58, CD16, CD32, CD64 and HLA-DR) and for their capacity to stimulate allogenic (MLR) or autologous (antigen presentation tests) lymphocytes. The results demonstrated that the mean recovery rates after freezing in liquid nitrogen or at -80 degrees C were (67 +/- 14)% and (71 +/- 13)% respectively, without any significant difference between the two techniques. The immunophenotype was not modified by the freezing-thawing procedure, as well as the lymphocyte stimulating capacities. In conclusion, our study showed that substantial numbers of functional DCs can be derived from peripheral blood monocytes using Teflon bags. DCs can be cryopreserved in a good laboratory practice setting for further clinical trials with an acceptable loss of cells and without modification of their functions.
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PMID:Cryopreservation of Dendritic Cells Grown in Vitro from Monocytes for Their Future Clinical Use. 1257 59

Dendritic cells (DCs) are powerful antigen-presenting cells that have the unique capacity to stimulate naive T-cells (1, 2). DCs are identified by a triad of criteria: Morphologically, they exhibit pronounced cytoplasmic veils that are mobile and can easily be observed under a phase-contrast microscope. These veils become apparent only in the mature state. Phenotypically, they express high levels of major histocompatibility class (MHC) (class I and II), adhesion (CD11c, CD54, CD58), and costimulatory (CD80, CD86, CD40) molecules on their cell surfaces. They also express CD1a and CD83, but lack CD14. On cytocentrifuge smears stained with anti-CD68, a marker of the endocytic system that is abundant in macrophages, DCs display spotlike staining whereas typical macrophages are strongly positive all over the cytoplasm. When looking at forward/side scatter profiles in the fluorescence-activated cell sorter (FACS), DCs show high light scattering and are outside the typical lymphocyte gate. Functionally, they are potent stimulators of resting T lymphocytes in the allogeneic mixed leukocyte reaction. DCs derived from various tissues have been shown to undergo a complex maturation process during which their morphology, phenotype, and function change. DCs are derived from bone marrow progenitors and circulate in the blood as immature precursors before they migrate into peripheral tissues, such as the epidermis, heart, lung, liver, gut, thymus, spleen, and lymph nodes. DCs of myeloid as well as of lymphoid origin have been described (3-5).
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PMID:Dendritic cells in old age. 2235 Dec 83


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