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)

Hyperplastic lymphoid tissues of the Waldeyer's ring in human immunodeficiency virus (HIV)-infected patients may occasionally contain multinucleated giant cells (MGCs). These cells, which are unrelated to any opportunistic infection, previously have been demonstrated to harbor significant amounts of HIV. Studies undertaken to characterize these MGCs have generated conflicting results: some reports suggested a macrophage origin, whereas others supported a dendritic cell lineage. This study was performed to determine the occurrence of MGCs in a series of adenoid/tonsil specimens from HIV-seropositive patients showing no histological evidence of opportunistic infection in order to further characterize the phenotype of these cells and to investigate the role of a viral infection in their pathogenesis. Adenoid/tonsil tissue specimens from 21 HIV-seropositive patients with no documented opportunistic infection were scrutinized for the presence of MGCs and evaluated immunohistochemically on paraffin sections by antibodies directed against various macrophage and DC antigens. These antigens included CD68, the macrophage marker 3A5, major histocompatibility complex Class II, S-100 protein, CD1a, and CD83. Additional immunostainings directed at CD21 and CD35 as well as at the HIV-associated p24 antigen were also performed. Finally, the presence of Epstein-Barr virus and human herpesvirus 8 viral sequences was investigated by in situ hybridization and by polymerase chain reaction analysis, respectively. MGCs were found in 14 patients (66.7%), regardless of gender, age, method of viral transmission, CD4 cell count, viral load, or ethnic group. These cells were mostly localized at the lymphoepithelium layer of the tonsillar crypts and, to a lesser extent, in the interfollicular areas of the underlying lymphoid tissue, which consistently exhibited features of follicular hyperplasia. Phenotypically, MGCs were found to be CD68+, 3A5+, major histocompatibility complex Class II+, S-100 protein+/-, CD1a-, CD21-, CD35-, and CD83-. Although the HIV-associated p24 protein was consistently present in the cytoplasm of these cells, no sign of Epstein-Barr virus or human herpesvirus 8 infection could be demonstrated. Consequently, our study didn't show any conclusive evidence to support that MGCs in hyperplastic lymphoid tissues of the Waldeyer's ring from HIV-seropositive patients originated from dendritic cells. The definite nature of these cells has yet to be elucidated, but it is plausible that they simply represent activated macrophages that are infected with HIV present in the oropharyngeal secretions during the circulation of their precursor through the lymphoepithelium area of adenoids and tonsils.
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PMID:HIV-associated multinucleated giant cells in lymphoid tissue of the Waldeyer's ring: a detailed study. 1114 25

We have attempted to improve retrovirus-mediated gene transfer efficacy into hematopoietic progenitor cells (HPCs) without causing them to lose their lymphoid potential. Highly purified CD34(+) cells on CH-296 fibronectin fragments have been transduced with three different cytokine combinations. Murine CD2 was used as a marker gene. Transgene expression was assayed by FACS analysis shortly after transduction of CD34(+) cells and after long-term culture (LTC) extended by differentiation of various lymphoid lineages: NK cells, B cells, and dendritic cells. Compared with the historical cytokine mix, i.e., SCF (stem cell factor) + IL-3 (interleukin 3) + IL-6, the combination SCF + FL (Flt-3 ligand) + M-GDF (megakaryocyte growth and differentiation factor) + IL-3 significantly improved the total number of viable cells and CD34(+) cells after transduction and the long term-cultured progenitors after 6 weeks. In addition, the combination of SCF + FL + M-GDF + IL-3 maintained more efficiently the lymphoid potential of the progeny of transduced long term-cultured CD34(+) cells, as attested by the significantly higher number of CD56(+), CD19(+), and CD1a(+) cells recovered when FL and M-GDF were added to SCF + IL-3. Thus, even though additional improvements may still be needed in transduction of HPCs, these conditions were adopted for a clinical trial of gene therapy for X-linked severe combined immunodeficiency.
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PMID:Optimization of retroviral gene transfer protocol to maintain the lymphoid potential of progenitor cells. 1117 65

Based on the relative expression of CD11c and CD1a, we previously identified subsets of dendritic cells (DCs) or DC precursors in human peripheral blood. A CD1a(+)/CD11c(+) population (CD11c(+) DCs), also called myeloid DCs, is an immediate precursor of Langerhans cells, whereas a CD1a(-)/CD11c(-) population (CD11c(-) DCs), sometimes called lymphoid DCs but better known as plasmacytoid DCs, is composed of type I IFN (IFN-alpha beta)-producing cells. Here, we investigate the effects of IFN-alpha beta and IFN-gamma as well as other cytokines on CD11c(+) and CD11c(-) DC subsets, directly isolated from the peripheral blood, instead of in vitro-generated DCs. IFN-gamma and IFN-alpha, rather than GM-CSF, were the most potent cytokines for enhancing the maturation of CD11c(+) DCs. Incubation of CD11c(+) DCs with IFN-gamma also resulted in increased IL-12 production, and this IL-12 allowed DCs to increase Th1 responses by alloreactive T cells. In contrast, IFN-alpha did not induce IL-12 but, rather, augmented IL-10 production. IFN-alpha-primed matured CD11c(+) DCs induced IL-10-producing regulatory T cells; however, this process was independent of the DC-derived IL-10. On the other hand, IFN-alpha by itself neither matured CD11c(-) DCs nor altered the polarization of responding T cells, although this cytokine was a potent survival factor for CD11c(-) DCs. Unlike IFN-alpha, IL-3 was a potent survival factor and induced the maturation of CD11c(-) DCs. The IL-3-primed CD11c(-) DCs activated T cells to produce IL-10, IFN-gamma, and IL-4. Thus, CD11c(+) and CD11c(-) DC subsets play distinct roles in the cytokine network, especially their responses to IFNs.
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PMID:Differential regulation of human blood dendritic cell subsets by IFNs. 1120 45

At the ISAC 2000 Congress, the Clinical Cytometry Society organized a meeting of international experts to reach consensus on the minimum number of antibodies required for a full evaluation of hematologic and lymphoid neoplasias. A questionnaire was distributed prior to the meeting to numerous experts from US and European institutions and 13 responses were received. At the meeting, 25 individuals, including most of those who returned responses, participated in the discussions and voted on the issues presented. In chronic lymphoproliferative disorders (CLD), 9 antibodies (anti-CD5, CD19, kappa, lambda, CD3, CD20, CD23, CD10, and CD45) were deemed essential for initial evaluation by 75% of the participants. There was near unanimity that additional markers (selected from CD22, FMC7, CD11c, CD103, CD38, CD25, CD79b and heavy chains for B-cell disorders, and CD4, CD7, CD8, CD2, CD56, CD16, TCRa/b, and TCRg/d for T-cell disorders) would be needed to fully characterize CLD, although not every marker would be useful in all cases. Tissue lymphomas were believed to be similar to CLD, needing a minimum of 12--16 markers. However, for some cases, CD30, bcl-2, TdT, CD71, CD1a, and CD34 were cited as useful by the participants. Markers mentioned for plasma cell disorders included kappa, lambda, CD38, CD45, CD56, CD19, CD20, CD138, and heavy chains. Of 17 voting participants, 16 agreed that between 5 to 8 markers would be essential reagents for plasma cell disorders. For acute leukemia (AL), 10 markers (CD10, CD19, CD13, CD33, CD34, CD45, CD7, CD14, CD3, and HLADR) were considered essential by 75% of participants for initial characterization of the leukemia lineage. Most (>75%) agreed that at least one more B (CD20, CD22, CD79a, IgM), T (CD1a, CD2, CD4, CD5, CD8), myeloid (CD11b, CD15, CD64, CD117, myeloperoxidase), erythroid (CD36, CD71, glycophorin A), and megakaryocytic (CD41, CD61) reagents should be included in the essential panel. However, there was no agreement as to which was optimal. Thus, approximately 13--15 of those reagents would be considered essential in all cases of AL, whereas others (CD16, CD56, CDw65, TdT, and cytoplasmic CD3) were mentioned as useful in some cases. Almost all voting participants believed that the appropriate number of markers for complete characterization of AL would average 20--24. The majority of the responders (11 of 13) indicated that fewer reagents could be used in monitoring or staging patients with previously characterized disease, but not all ventured a specific number of reagents. From the above results, we conclude that the phenotypic analysis of hematologic and lymphoid neoplasia requires a rather extensive panel of reagents. Supplementary reagents might even be necessary if they prove to become relevant for diagnostic purposes. Reducing the number of antibodies could significantly compromise the diagnostic accuracy, appropriate monitoring, or therapy of these disorders.
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PMID:Optimal number of reagents required to evaluate hematolymphoid neoplasias: results of an international consensus meeting. 1124 3

Skin lesions of dermatophytosis are thought to be a result of a T cell-dependent inflammatory response that is mediated by various cytokines. We examined whether IFN-gamma-positive cells (as expression of Th1 response) were present in the skin lesions of dermatophytosis in situ by immunohistochemical techniques. Mixtures of CD4-positive T cells and CD8-positive T cells were found to be present in the dermal infiltrates of the lesions. Considerable numbers of CD1a-positive cells were detected in the upper dermis and epidermis. A marked accumulation of CD68-positive cells was found in the upper dermis. IFN-gamma-positive cells were present in the upper dermis of the lesions. The pattern of IFN-gamma staining appeared to be intracellular in mononuclear lymphoid cells. The staining was considered to be highly specific because it could be completely blocked by preabsorption with recombinant IFN-gamma. Our data support the hypothesis that the skin lesions of dermatophytosis may be associated with a Th1 response. Th1 response, which is characterized by IFN-gamma release, is thought to be involved in the host defense against dermatophytes and to reflect cutaneous reaction in dermatophytosis.
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PMID:Immunohistochemical detection of interferon-gamma-producing cells in dermatophytosis. 1127 3

The identification of immunophenotypic markers with restricted expression has long been a critical issue in diagnostic and therapeutic advances for acute leukemias. We previously developed a monoclonal antibody against a new thymocyte surface antigen, JL1, and showed that JL1 is expressed in the majority of acute leukemia cases. In this study, using multiparameter flow cytometric analyses, we found that JL1 was uniquely expressed in subpopulations of normal bone marrow (BM) cells, implying the association of JL1 with the differentiation and maturation process. Although CD34(+) CD10(+) lymphoid precursors and some of maturing myeloid cells express JL1, neither CD34(+) CD38(-/lo) nor CD34(+) AC133(+) noncommitted pluripotent stem cells do. As for the myeloid precursors, CD34(+) CD33(+) cells do not express JL1. During lymphopoiesis, JL1 on the earliest lymphoid precursors disappear in the CD20(+) sIgM(+) stage of B-cell development or after CD1a down-regulation in thymocytes. Despite the highly restricted expression of JL1 in normal BM cells, most of the leukemias express JL1 irrespective of their immunophenotypes. These results indicate that JL1 is not only a novel differentiation antigen of hematopoietic cells, but also a leukemia-associated antigen. Therefore, we suggest that JL1 be a candidate molecule in acute leukemia for the diagnosis and immunotherapy that spares the normal BM stem cells.
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PMID:Expression of leukemia-associated antigen, JL1, in bone marrow and thymus. 1129 May 65

To better define the clinical and pathologic features of interdigitating dendritic cell sarcoma (IDCS), we report 4 cases, including the first reported in the tonsil. There were 2 male and 2 female patients (mean age, 70 years). Sites of tumor included 1 case each in the right cervical lymph node, left axillary lymph node, right tonsil, and right inguinal lymph node. Histologically, all showed diffuse effacement of the lymphoid tissue by pleomorphic round to spindled cells with convoluted nuclei and abundant eosinophilic cytoplasm. All were immunoreactive for S-100, CD68, lysozyme, and vimentin. CD45 was positive in 3 cases and CD1a in 1 case. Fascin was positive in 3 cases. Other immunostains, including CD3, CD20, CD21, CD30, actin, cytokeratin, and HMB-45, were negative. Ultrastructurally, the tumor cells were elongated and showed indented nuclei, variable numbers of lysosomes, and interdigitating cytoplasmic processes. Follow-up was available for all cases. One patient died of widespread disease 2 months after diagnosis. One was alive with metastatic lung disease at 12 months. Two patients were disease free at 5 and 9 months.
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PMID:Interdigitating dendritic cell sarcoma. A report of four cases and review of the literature. 1129 8

Human dendritic cell (DC) precursors were engrafted and maintained in NOD/SCID- human chimeric mice (NOD/SCID-hu mice) implanted with human cord blood mononuclear cells, although no mature human DCs were detected in lymphoid organs of the mice. Two months after implantation, bone marrow (BM) cells of NOD/SCID-hu mice formed colonies showing DC morphology and expressing CD1a in methylcellulose culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-alpha). The CD34-/CD4+/HLA-DR+ cell fraction in NOD/SCID-hu mouse BM generated CD1a(+) cells that were highly stimulatory in mixed leukocyte reactions in culture with GM-CSF and TNF-alpha. These results suggest a strong potential for NOD/SCID-hu BM to generate human DCs, although DC differentiation may be blocked at the CD34-/CD4+/HLA-DR+ stage. (Blood. 2001;97:3655-3657)
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PMID:Arrest of human dendritic cells at the CD34-/CD4+/HLA-DR+ stage in the bone marrow of NOD/SCID-human chimeric mice. 1136 65

Previous studies have analyzed the lymphoid and myeloid foci within the gingival mucosa in health and chronic periodontitis (CP); however, the principal APCs responsible for the formation and organizational structure of these foci in CP have not been defined. We show that in human CP tissues, CD1a(+) immature Langerhans cells predominantly infiltrate the gingival epithelium, whereas CD83(+) mature dendritic cells (DCs) specifically infiltrate the CD4(+) lymphoid-rich lamina propria. In vivo evidence shows that exacerbation of CP results in increased levels of proinflammatory cytokines that mediate DC activation/maturation, but also of counterregulatory cytokines that may prevent a Th-polarized response. Consistently, in vitro-generated monocyte-derived DCs pulsed with Porphyromonas gingivalis strain 381 or its LPS undergo maturation, up-regulate accessory molecules, and release proinflammatory (IL-1beta, PGE(2)) and Th (IL-10, IL-12) cytokines. Interestingly, the IL-10:IL-12 ratio elicited from P. gingivalis-pulsed DCs was 3-fold higher than that from Escherichia coli-pulsed DCs. This may account for the significantly (p < 0.05) lower proliferation of autologous CD4(+) T cells and reduced release of IFN-gamma elicited by P. gingivalis-pulsed DCs. Taken together, these findings suggest a previously unreported mechanism for the pathophysiology of CP, involving the activation and in situ maturation of DCs by the oral pathogen P. gingivalis, leading to release of counterregulatory cytokines and the formation of T cell-DC foci.
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PMID:Mature dendritic cells infiltrate the T cell-rich region of oral mucosa in chronic periodontitis: in situ, in vivo, and in vitro studies. 1159

Dendritic cells (DCs) are a heterogeneous population of antigen-presenting cells (APCs) identified in various tissues, including the skin (Langerhans cells), lymph nodes (interdigitating and follicular DCs), spleen, and thymus. Properties of DCs include the ability to (1) capture, process, and present foreign antigens; (2) migrate to lymphoid-rich tissue; and (3) stimulate innate and adaptive antigen-specific immune responses. Until recently, the ability to study DCs has been limited by their absence in most culture systems. It is now known that specific cytokines can be used to expand DCs to numbers sufficient for their in vitro evaluation and for their use in human immunotherapy trials. Human DCs can be derived from hematopoietic progenitors (CD34+-derived DCs) or from adherent peripheral blood monocytes (monocyte-derived DCs). Cultured DCs can be recognized by a typical veiled morphologic appearance and expression of surface markers that include major histocompatibility complex class II, CD86/B7.2, CD80/B7.1, CD83, and CD1a. DCs are susceptible to a variety of gene transfer protocols, which can be used to enhance biological function in vivo. Transduction of DCs with genes for defined tumor antigens results in sustained protein expression and presentation of multiple tumor peptides to host T cells. Alternatively, DCs may be transduced with genes for chemokines or immunostimulatory cytokines. Although the combination of ex vivo DC expansion and gene transfer is relatively new, preliminary studies suggest that injection of genetically modified autologous DCs may be capable of generating anti-tumor immune responses in patients with cancer. Preclinical animal studies showing potent antigen-specific tumor immunity after DC-based vaccination support this hypothesis and provide rationale to further evaluate this approach in patients. Preliminary human studies are now required to evaluate optimal DC dose, schedule of vaccination, route of delivery, and maturational state of cultured cells. Initiation of these phase I/II cell therapy-based studies will occur in collaboration with hospital-based transfusion facilities. Issues relating to cell harvesting, storage, culture methodology, and administration require the collaborative efforts of basic scientists, immunologists, clinical investigators, and transfusion medicine staff to ensure strict quality control of injected cellular products. This review is intended to provide a brief overview of clinical DC-based gene transfer.
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PMID:Genetically modified dendritic cells in cancer therapy: implications for transfusion medicine. 1166 36


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