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)

Dendritic cells (DC) are potent APCs that sample Ags from the surrounding environment and present them to naive T cells using cell surface Ag-presenting molecules. The DC in both lymphoid and nonlymphoid tissues express high levels of CD1, a cell surface glycoprotein capable of presenting lipids and glycolipids to T cells. Distinct group 1 CD1 isoforms (CD1a, -b, -c) in man are known to traffic to different parts of the endocytic system where microbial Ags may be sampled. Guinea pigs are the only known rodent species that express the group 1 CD1 proteins. Therefore, we examined the expression and trafficking of guinea pig CD1 (gpCD1) isoforms on isolated DC. Confocal microscopy using mAbs specific for individual gpCD1 isoforms revealed differential trafficking of two distinct CD1b isoforms within DC. Colocalization of MHC class II was observed with the gpCD1b1 isoform, consistent with localization in the late endosomes of DC. In contrast, the gpCD1b3 isoform lacks an endosomal sorting motif and remains on the cell surface. Following incubation with Mycobacterium tuberculosis lipoarabinomannan, colocalization of endocytosed lipoarabinomannan with the gpCD1b1 isoform was observed but not with the gpCD1b3 isoform, which remained primarily on the cell surface. These data demonstrate that guinea pig DC express CD1 isoforms with unique trafficking patterns that recapitulate the patterns seen for human CD1 isoforms. This suggests evolutionary pressure for a conserved mechanism in mammals that allows CD1 to sample lipid Ags from various subcompartments of the endocytic system.
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PMID:Conservation of CD1 intracellular trafficking patterns between mammalian species. 1247 Nov 29

Establishment of an assay capable of generating all classes of human lymphocytes from hematopoietic stem cells (HSCs) will provide new insight into the mechanism of human lymphopoiesis. We report ontogenic, functional, and histologic examination results of reconstituted human lymphocytes in NOD/SCID/ gammacnull mice after the transplantation of human cord blood (CB) CD34+ cells. After transplantation, human B, natural killer (NK), and T cells were invariably identified in these mice, even though no human tissues were cotransplanted. Immature B cells resided mainly in bone marrow (BM), whereas mature B cells with surface immunoglobulins were preferentially found in spleen. NK cells were identified in BM and spleen. T cells were observed in various lymphoid organs, but serial examinations after transplantation confirmed human T lymphopoiesis occurring in the thymus. These human lymphocytes were also functionally competent. Human immunoglobulin M (IgM), IgA, and IgG were detected in the sera of these mice. T cells showed a diverse repertoire of T-cell-receptor Vbeta (TCR Vbeta) chains, proliferated in response to phytohemagglutinin, and were cytotoxic against cell lines. NK activity was demonstrated using the K562 cell line. Immunohistochemical analysis revealed that human lymphocytes formed organized structures in spleen and thymus that were analogous to those seen in humans. In the thymus, CD4 and CD8 double-positive T cells were predominant and coexpressed CD1a and Ki-67, thereby supporting the notion that T lymphopoiesis was taking place. NOD/SCID/ gammacnull mice provide a unique model to investigate human lymphopoiesis without the cotransplantation of human tissues.
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PMID:Complete reconstitution of human lymphocytes from cord blood CD34+ cells using the NOD/SCID/gammacnull mice model. 1268 24

The study of hematopoietic stem cells (HSCs) and the process by which they differentiate into committed progenitors has been hampered by the lack of in vitro clonal assays that can support erythroid, myeloid and lymphoid differentiation. We describe a method for the isolation from human fetal liver of highly purified candidate HSCs and progenitors based on the phenotypes CD38(-)CD34(++) and CD38(+)CD34(++), respectively. We also describe a method for the growth of colony-forming cells (CFCs) from these cell populations, under defined culture conditions, that supports the differentiation of erythroid, CD14/CD15(+) myeloid, CD1a(+) dendritic cell and CD56(+) NK cell lineages. Flow cytometric analyses of individual colonies demonstrate that CFCs with erythroid, myeloid and lymphoid potential are distributed among both the CD38(-) and CD38(+) populations of CD34(++) progenitors.
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PMID:Isolation, growth and identification of colony-forming cells with erythroid, myeloid, dendritic cell and NK-cell potential from human fetal liver. 1273 73

Conjunctival lymphoid follicles (CLFs), present in normal individuals, undergo hyperplasia upon conjunctival infection by a specific array of pathogens; infection-associated enlargement of draining preauricular lymph nodes suggests that conjunctival follicles participate in the afferent limb of acquired immune responses for the ocular surface. The present study was performed to delineate the structural and lymphoid anatomy of CLFs in the baboon (Papio anubis), a non-human primate conjunctival model with close similarity to the human. Conjunctiva from both eyes, along with mesenteric lymph node, spleen, tonsil, and ileum controls were harvested from ten baboons at necropsy, and studied by histochemical and immunohistochemical methods. Baboon conjunctival follicles were identified as dense oval collections of leukocytes in the substantia propria with infiltration into a thinned overlying conjunctival epithelium. Goblet cells were universally absent, the overlying mucin layer was attenuated, and the follicle-associated epithelium (FAE) demonstrated comparatively diminished alkaline phosphatase expression. The basement membrane overlying each follicle appeared discontinuous. CD4-positive T lymphocytes were distributed in parafollicular areas and to a lesser degree in follicle germinal centers. B lymphocytes formed the predominant cell in follicles, and also heavily infiltrated the FAE. B cell IgM expression was prominent in germinal centers, while IgD staining occurred in a horseshoe-shaped distribution in the follicle mantle zone. Although B cell IgA expression was noted in the non-follicular conjunctiva, IgA expression was inconspicuous within conjunctival follicles. S-100- and CD1a-positive dendritic cells were found in FAE, while fascin-positive mature dendritic cells appeared in the deeper areas of each follicle. CD68-positive macrophages were dispersed throughout the follicles. CD35-positive follicular dendritic cells were observed only in germinal centers. CLFs appear highly organized consistent with a role in the adaptive immune response to conjunctival pathogens.
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PMID:Structural and cellular architecture of conjunctival lymphoid follicles in the baboon (Papio anubis). 1274 51

The lymph node is the site of antigen presentation, and dendritic cells are sentinels for anti-tumor immunity. However, little is known about the histological features of lymph nodes and dendritic cells in soft tissue sarcomas. The reactive lymph node and infiltration of dendritic cells or effector cells were studied histologically in 10 soft tissue sarcomas with reactive lymphoid hyperplasia. The cases included four malignant fibrous histiocytomas, two malignant peripheral nerve sheath tumors, one synovial sarcoma, one epithelioid sarcoma, one malignant granular cell tumor, and one liposarcoma. The proportions of the T zone, lymphoid follicle, and lymphoid sinus (which was occupied by cells immunopositive for antibodies against CD3, CD20, or CD68) were 33.4% +/- 11.0%, 6.1% +/- 4.9%, and 13.5% +/- 6.5%, respectively. T zone hyperplasia was observed in all cases, and sinus histiocytosis was found in four. The proportion of the T zone in regional lymph nodes of soft tissue sarcoma patients was significantly higher than that in adult autopsy cases without a cancer history. CD8-, TIA-1-, or granzyme B-positive effector cells were found in each sarcoma tissue. Whereas CD1a-positive dendritic cells were not detected, S-100 protein-positive or CD83-positive dendritic cells were observed in five sarcoma tissues. The coefficient correlation between the numbers of effector cells and dendritic cells positive for CD83 or S-100 protein were demonstrated. Although this is a preliminary report, the present study demonstrated that some soft tissue sarcoma patients showed reactive lymphoid hyperplasia. Furthermore, the association between the infiltration of dendritic cells and that of effector cells was observed in patients with soft tissue sarcomas.
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PMID:Dendritic cell and effector cell infiltration in soft tissue sarcomas with reactive lymphoid hyperplasia. 1455 33

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare malignancy derived from professional antigen presenting cells. This report describes a case of IDCS arising in the salivary gland associated lymphoid tissue of the parotid gland of a 51 year woman, presenting with a painless neck swelling. Histologically, sheets of S100(+)/Ccd68(+)/CD45(+)/CD34(-)/CD1a(-) spindle cells were surrounded with an inflammatory infiltrate with no evidence of B or T cell clonal proliferations. No evidence of either human herpesvirus 8 or Epstein-Barr virus could be detected by quantitative polymerase chain reaction in the tumour cells with serological evidence of previous Epstein-Barr virus infection. The patient remains well and disease free 24 months after presentation without specific treatment.
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PMID:Interdigitating dendritic cell sarcoma of salivary gland associated lymphoid tissue not associated with HHV-8 or EBV infection. 1469 45

Dendritic cells (DCs) are present in essentially every mammalian tissue, where they operate at the interface of innate and acquired immunity by recognizing pathogens and presenting pathogen-derived peptides to T lymphocytes. According to the research group of Shortman, experimental results suggest a "dual" DC differentiation model, demonstrating the existence of both myeloid-derived (with characteristic IF: CD11b+, CD11c+, CD8alpha- and DEC205+) and lymphoid-derived DCs (showing CD11b- CD11c-, CD8alpha+ and DEC205+ IF). DCs, including interdigitating cells (IDCs) and Langerhans cells (LCs), are characterized by dendritic morphology, high migratory mobility and are the most effective, "professional" cells for antigen presentation in primary immune responses. Most of the DCs express immunocytochemically detectable antigens like: S-100, CD1a, CD40 receptor, adhesion molecules (ICAM-1 or CD54, LFA-1 and LFA-3), integrins (CD11a, CD11c and CD18), CD45, CD54, co-stimulatory molecules (B7-1 or CD80, B7-2 or CD86), F418, MHC class I and II and DEC-205, multilectin receptor, immunostimulatory cytokine (IL-12) and, of course, Fc and complement receptors. Following recognition and uptake of antigens, mature dendritic cells (DCs) migrate to the T lymphocyte rich area of draining lymph nodes, display an array of antigen-derived peptides on the surface of major histocompatibility complex (MHC) molecules and acquire the cellular specialization to select and activate naive antigen-specific T lymphocytes. Immunotherapeutic ideas are based on the ability of the mammalian immune system to recognize neoplastically transformed cells. Immunotherapy of human neoplasms has always represented a very attractive fourth-modality therapeutic approach, especially in light of the many shortcomings of conventional surgical, radiation and chemotherapies in the management of neoplastically transformed cells. The cancer vaccine approach to therapy is based on the notion that the immune system could possibly mount a rejection strength response against the neoplastic cell conglomerate. The efficiency of DCs for T lymphocyte stimulation moved a number of research groups to develop DC- based immunotherapy approaches. The failure of cancer vaccines may be attributed to the relationship between host and neoplasm: through a natural selection process, the host facilitates the selective enrichment of clones with highly aggressive neoplastically transformed cells, being in various stages of differentiation and only during certain stages express neoplastic cell specific molecules.
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PMID:Antigen presentation by dendritic cells and their significance in antineoplastic immunotherapy. 1501 56

A 77-year-old woman presented to the outpatient hematology clinic in August 2001 with leukocytosis, recurrent bacterial infections, sweating and weight loss. Bone marrow biopsy showed 80% infiltration with lymphoid cells having a prolymphocytic morphology. Flow-cytometric immunophenotype analysis showed that over 80% of the cells were positive for CD2, CD3, CD4, CD5 and CD7 antigens and negative for terminal deoxynucleotidyl transferase and CD1a antigens. T cell prolymphocytic leukemia (T-PLL) was diagnosed on the basis of these findings. The diagnosis was later confirmed by cytogenetic analysis and fluorescence in situ hibridization. The patient had the following karyotype: 46,X,der(X)t(X;3) (q28;p25) t(X;16)(p14;q12), der(3) t(X;3)(q28;p25), der(6) t (X;6) (p14;q25), (8) (q10), del(11) (q14q23), der(13) t (5;13) (q34;p11), der(13) t(13;14)(q22;q11), inv(14)(q11q32), der (16) t(X;16)(q28;q12), r(17)(p13q21), der(20) t(17;20) (q21; q13),22p+. The cytogenetic rearrangements der(6)t(X;6) (p14;q25), der(13)t(13;14)(q22;q11),t(5;13)(q34;p11), r(17) (p13q21) and t(17;20)(q21;q13) have not been described previously in the literature in patients with T-PLL.
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PMID:T cell prolymphocytic leukemia with new chromosome rearrangements. 1503 40

The aim of this study was to compare the cellular composition and organization of rheumatoid (RA) synovium, which has several of the characteristics of lymphoid organs, with lymph nodes. To clarify further whether RA synovium can be classified as an ectopic lymphoid organ, paired RA synovium and lymph node (LN) tissues from 11 patients were compared in terms of T-cell-B-cell and germinal centre (GC) organization, dendritic cell (DC) subsets, and chemokine expression. Tonsil, a normal secondary lymphoid organ, was used as a tissue control. In paired RA LN and synovium, more follicular DC-positive GCs were observed in LN, but when observed in synovium, they shared the same T-cell-B-cell organization and mean GC size. In LN, a predominance of mature DC-LAMP-positive DCs of myeloid (CD11c-positive) or lymphoid (CD123-positive) origin was observed, whereas paired RA synovium was characterized by the relative accumulation of immature CD1a-positive DCs. In the same way, CCL19-CCL21/CCR7, a chemokine/chemokine receptor complex involved in mature DC migration, was more frequently seen in LN than in paired RA synovium. In synovium, such expression was associated with lymphoid follicle formation, with or without a GC. Conversely, CCL20, a chemokine involved in immature DC migration, was expressed in RA synovium and tonsils but not in paired LNs. In conclusion, although similarities were observed, this study, using paired samples, indicates that the RA synovium lacks some of the features that are characteristic of a lymphoid organ.
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PMID:Paired synovium and lymph nodes from rheumatoid arthritis patients differ in dendritic cell and chemokine expression. 1530 35

Myelodysplastic syndromes (MDS) are clonal stem cell disorders, characterized by ineffective and dysplastic hematopoiesis. MDS patients have a defective immune response manifested by increased susceptibility to bacterial infections, autoimmune phenomena, and high incidence of lymphoid malignancies. Presently, we investigated the phenotype and function of monocyte-derived dendritic cells (MoDC) in 23 MDS patients and 15 controls at different stages of differentiation using the maturation stimuli tumor necrosis factor-alpha (TNF-alpha) and LPS. Monocytes from MDS patients showed low potential to differentiate into dendritic cells (DC), as determined by low cell yield and CD1a expression. MDS-MoDCs exhibited low expression of mannose receptor and reduced endocytic capacity. MDS-MoDCs showed a diminished response to TNF-alpha with low CD83, CD80, and CD54 expression and allostimulatory capacity. In patients with 5q syndrome, monocytes and MoDCs were positive for the 5q deletion, suggesting their origin from the malignant clone. Our data indicate that MoDCs in MDS display quantitative and functional abnormalities that may contribute to the defective immune response of these patients.
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PMID:Defective tumor necrosis factor alpha-induced maturation of monocyte-derived dendritic cells in patients with myelodysplastic syndromes. 1550 96


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