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)

This study assessed the immunological and clinical responses of women with human papillomavirus (HPV) 16-associated high-grade vulval intraepithelial neoplasia (VIN) vaccinated with TA-HPV, a recombinant vaccinia virus encoding modified HPV 16 and 18 E6 and E7. Eighteen women with HPV 16-positive high-grade VIN were vaccinated with TA-HPV. The extent of their baseline disease was compared after 24 weeks by lesion measurements and histological analysis. Viral load was assessed pre- and postvaccination by real time PCR. Cell-mediated immunity to HPV 16 E6 and/or E7 peptides (HLA-A2 epitopes) or vaccinia-infected cell lysates was determined by IFN-gamma enzyme-linked immunospot (ELISPOT) and T cell proliferation using an HPV 16 L2E6E7 fusion protein. Antibodies were measured by ELISA using vaccinia-infected cell lysates or HPV 16 and 18 E6 and E7 glutathione S-transferase-fusion proteins. Lesion-infiltrating CD4(+), CD8(+), CD1a(+), and CD68(+) immune cells were assessed by immunohistochemistry. The single vaccination with TA-HPV was well tolerated, and all patients showed an increased ELISPOT and/or antibody response to vaccinia. There were significant differences in HPV-16 E7-specific ELISPOT and L2E6E7 proliferative responses in the patients at one or more time points postvaccination as compared with the prevaccination status; two patients showed transient increased antibody responses. Overall, 13 women showed an increased HPV 16-specific immune response by one or more methodologies after immunization. Eight patients demonstrated a reduction in lesion diameter of at least 50% and a further four patients showed significant symptom relief. Viral load was reduced or cleared in six of eight lesion responders but also in six of ten nonresponders. Before vaccination, clinical responders had significantly higher levels of lesion-associated CD4(+), CD8(+), and CD1a(+)-immune cells than nonresponders. There were no differences in CD68 (macrophages) between responders and nonresponders before or after vaccination. Nonresponders did show a significant increase in CD4(+)- and CD8(+)- but not CD1a(+)-immune cells postvaccination but at lower levels overall than responder patients. Local immune infiltration may be a critical factor in potential responsiveness to vaccine therapy in HPV-associated neoplasia and should be carefully monitored in future placebo-controlled trials of immunotherapy for VIN.
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PMID:Immunological and clinical responses in women with vulval intraepithelial neoplasia vaccinated with a vaccinia virus encoding human papillomavirus 16/18 oncoproteins. 1452 32

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

Downregulation of major histocompatibility complex (MHC) class I, MHC-II, and intercellular adhesion molecule 1 (ICAM-1) expression in infected cell lines allows some viruses to escape host immunity. In skin lesions of varicella zoster virus (VZV), MHC-II transcripts were demonstrated in keratinocytes around vesicles, but not in VZV-infected cells. Whether other immunoevasive mechanisms are present during herpes zoster (HZ) is not yet elucidated. The aim of the study was to disclose the temporal immunohistochemical expression of immune escape mechanisms during HZ. Sequential skin biopsies were performed in 5 HZ patients. VZV IE63, CD1a, CD3, CD4, CD8, CD56, CD68, L1, HLA-DR, HLA-ABC, interleukin (IL)-6, IL-10, interferon gamma (IFNgamma), tumor necrosis factor alpha (TNFalpha), and ICAM-1 expressions were assessed on frozen sections using immunohistochemistry. Controls consisted of normal skin, herpes simplex virus (HSV) skin infections, and other distinct bullous skin diseases. HLA-DR and ICAM-1 expressions were not observed in VZV- and HSV-infected keratinocytes, contrasting with their upregulation in the surrounding epidermis and inside nonviral blisters. However, HLA-ABC expressions were not inhibited in VZV-infected keratinocytes. Furthermore, the CD4/CD8 ratio remained unmodified during the infection evolution, and this ratio was variable among patients. Increased IFNgamma, TNFalpha, and IL-6 expressions were present, but IL-10 expression only increased in later stages. In contrast to in vitro MHC-I and MHC-II downregulation, VZV infection is related to MHC-II but not MHC-I expression on infected keratinocytes. The absence of ICAM-1 expression on infected keratinocytes may reduce their antigen presentation capacities to LFA-1 ligand-bearing T cells. This may represent another VZV-associated immune escape mechanism. Increased IFNgamma, TNFalpha, and IL-6 expressions suggest a TH1 profile.
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PMID:Absence of intercellular adhesion molecule 1 expression in varicella zoster virus-infected keratinocytes during herpes zoster: another immune evasion strategy? 1472 20

Annular lichen planus is a rare, unique subtype of lichen planus. We report a 34-year-old Japanese male who had multiple, dark red to purple, annular macules with slightly raised borders. Histopathological examination of a skin biopsy specimen from the peripheral region of the macule showed the typical features of lichen planus. Immunohistochemical stainings revealed that a number of CD1a-positive, S-100-protein-positive Langerhans cells were present at the border zone of the annular lesion and most of the infiltrating cells were CD4-positive, CD8-negative lymphocytes. Conversely, inside the annular lesion, the number of Langerhans cells was decreased, and an equal number of CD4-positive cells and CD8-positive cells was present in the sparse infiltration. These results suggest that activation of Langerhans cells initiated a lichenoid tissue reaction but a subsequent depletion of Langerhans cells suppressed the lymphocyte infiltration. These sequential events might be involved in the formation of the unique annular structure in this condition.
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PMID:Annular lichen planus: study of the cellular mechanisms of annularity. 1517 17

As human papillomavirus-like particles (HPV-VLP) represent a promising vaccine delivery vehicle, delineation of the interaction of VLP with professional APC should improve vaccine development. Differences in the capacity of VLP to signal dendritic cells (DC) and Langerhans cells (LC) have been demonstrated, and evidence has been presented for both clathrin-coated pits and proteoglycans (PG) in the uptake pathway of VLP into epithelial cells. Therefore, we compared HPV-VLP uptake mechanisms in human monocyte-derived DC and LC, and their ability to cross-present HPV VLP-associated antigen in the MHC class I pathway. DC and LC each took up virus-like particles (VLP). DC uptake of and signalling by VLP was inhibited by amiloride or cytochalasin D (CCD), but not by filipin treatment, and was blocked by several sulfated and non-sulfated polysaccharides and anti-CD16. In contrast, LC uptake was inhibited only by filipin, and VLP in LC were associated with caveolin, langerin, and CD1a. These data suggest fundamentally different routes of VLP uptake by DC and LC. Despite these differences, VLP taken up by DC and LC were each able to prime naive CD8(+) T cells and induce cytolytic effector T cells in vitro.
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PMID:Despite differences between dendritic cells and Langerhans cells in the mechanism of papillomavirus-like particle antigen uptake, both cells cross-prime T cells. 1520 17

Although dendritic cells (DCs) play an important role in tumor immunity, there have been no reports on their role in cholangiocellular carcinoma (CCC). In 26 formalin-fixed, paraffin-embedded tissue sections from patients with CCC, cells positive for CD83 (a marker of mature DCs), CD1a (a marker of immature DCs), and CD8 and CD4 (T cell markers) were counted, and expression of glucose-regulated protein (grp) 94, which is considered to participate in the maturation of DCs, was evaluated by immunohistochemistry and Western blot analysis to study the relationship between their expression and patients' disease outcome. The number of CD83-positive DCs at the invasive margin of CCCs correlated significantly with the number of CD8-positive or CD4-positive T cells in the cancerous region and was significantly higher in grp94-positive cancer than in grp94-negative cancer (P = 0.0006). CD83-positive patients (positive cells in invasive margin > 12.4/field) had both a significantly lower incidence of lymph node metastasis (23.1% vs 69.2%; P = 0.0206) and a better outcome than CD83-negative patients (P <0.001). We conclude that mature DCs are distributed predominantly at the invasive margin of cancers, and a significantly higher number of mature DCs at the invasive margin are observed in patients with grp94-positive cancer cells. Mature DCs may enhance CD8- and CD4-positive cell infiltration into cancers and improve prognosis in patients with CCC, due in part to abatement of lymph node metastasis.
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PMID:Dendritic cells, T-cell infiltration, and Grp94 expression in cholangiocellular carcinoma. 1525 53

The aims of this study were to analyze the composition of umbilical cord blood cells (UCBC), to examine the characteristics of dendritic cells (DC) before and after culture, to search the method of differentiation and increase of DC in vitro and to appraise surface antigen from UCBC. Twelve units of umbilical cord blood were collected from May 2002 to September 2002. Peripheral blood mononuclear cells of 9 cases were collected from healthy adult donors. The nature of UCBC was freshly determined and then UCBC were cultured for 1, 2, 3 and 4 weeks with granulocyte-monocyte colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), recombinant human stem cell factor (SCF) and EPO. Method of flow cytometry was used to determine the number of DC and cell surface antigens before and after culture by using monoclonal antibodies. The monoclonal antibodies included CD4, CD8, CD19, CD34, CD38, CD83, CD1a, CD11c and CDw123. The results showed that amounts of CD34+ progenitors in peripheral blood cells were 0.02 x 10(5)/ml, and amounts of CD34+ progenitors in human UCBC were 0.22 x 10(5)/ml. UCBC cultured for 1, 2, 3 and 4 weeks with GM-CSF, IL-3, EPO and SCF were shown to differentiate into CD1a+ CD11c+ CD83+ CDw123+ DC. Numbers of DC from UCBC remarkably generated in 2-4 weeks and then decreased in number. By culture with cytokines DC increased up to (10.6 - 28.2) x 10(5)/ml in actual numbers. It is concluded that the mononuclear cells of UCB are able to differentiate into CD1a+, CD83+, CD11c+ and CDw123+ DC when UCBC are cultured with proper cytokines of GM-CSF, SCF, EPO and IL-3 for 2-4 weeks. These DCs as antigen presenting cells are possibly effective in cancer immunotherapy.
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PMID:[Differentiation and increase of dendritic cells from umbilical cord blood in vitro]. 1549 21

A major problem after clinical hematopoietic stem cell transplantations is poor T-cell reconstitution. Studying the mechanisms underlying this concern is hampered, because experimental transplantation of human stem and progenitor cells into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice usually results in low T-lymphocyte reconstitution. Because tumor necrosis factor alpha (TNFalpha) has been proposed to play a role in T-lineage commitment and differentiation in vitro, we investigated its potential to augment human T-cell development in vivo. Administration of TNF to irradiated NOD/SCID mice before transplantation of human mononuclear cells from either cord blood or adult G-CSF-mobilized peripheral blood (MPBL) led 2-3 weeks after transplantation to the emergence of human immature CD4(+)CD8(+) double-positive T-cells in the bone marrow (BM), spleen, and thymus, and in this organ, the human cells also express CD1a marker. One to 2 weeks later, single-positive CD4(+) and CD8(+) cells expressing heterogenous T-cell receptor alpha beta were detected in all three organs. These cells were also capable of migrating through the blood circulation. Interestingly, human T-cell development in these mice was associated with a significant reduction in immature lymphoid human CD19(+) B cells and natural killer progenitors in the murine BM. The human T cells were mostly derived from the transplanted immature CD34(+) cells. This study demonstrates the potential of TNF to rapidly augment human T lymphopoiesis in vivo and also provides clinically relevant evidence for this process with adult MPBL progenitors.
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PMID:Tumor necrosis factor promotes human T-cell development in nonobese diabetic/severe combined immunodeficient mice. 1553 98

To investigate whether therapy with alpha interferon (IFN-alpha) induces changes in intrahepatic antigen-presenting cells (APCs), we obtained liver biopsy specimens before, during, and after therapy with IFN-alpha from chronic hepatitis B patients whose viral load had already been reduced by at least 8 weeks of treatment with lamivudine. HLA-DR, CD1a, and CD83 were not modified by the therapy. The intralobular expression of CD68 on Kupffer cells remained stable, denoting no changes in the number of resident macrophages during IFN-alpha treatment. In contrast, CD14 was weakly expressed in the absence of IFN-alpha and was significantly up-regulated during therapy. At the same time, the levels of soluble CD14 and interleukin-10 in plasma increased significantly. In vitro, monocytes maintained in the presence of IFN-alpha differentiated into macrophages or dendritic cells with higher levels of expression of CD14 than that for the control cultures. During therapy with IFN-alpha, T-cell infiltration in the portal spaces was reduced, mainly due to a significant decrease in the number of CD8(+) T cells. These findings show that IFN-alpha is biologically active on APCs in vivo and in vitro and suggest that this newly described regulatory function, together with the already known inhibitory effects on lymphocytes, may cooperate to reduce inflammation and consequent tissue damage in patients with chronic viral hepatitis.
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PMID:Antiviral treatment with alpha interferon up-regulates CD14 on liver macrophages and its soluble form in patients with chronic hepatitis B. 1567 38

CNS involvement in Langerhans cell histiocytosis (LCH) is a rare but potentially devastating disorder. Different types of involvement have been described by MRI. CNS changes can have space-occupying or degenerative character. Little is known about the underlying neuropathology and pathophysiology. In our study we reviewed brain samples from 12 patients with LCH. The neuropathology findings were correlated with the MR morphology and the clinical presentation. By neuropathology, three types of lesions were distinguished. (i) Circumscribed granulomas within the brain's connective tissue space corresponded to tumorous lesions in the meninges or choroid plexus on MRI. They showed a composition similar to Langerhans granulomas in peripheral organs, with variable presence of CD1a-reactive cells and pronounced CD8-positive (+) T-cell infiltration. (ii) Granulomas occur within the brain's connective tissue spaces with partial infiltration of the surrounding CNS parenchyma by CD1a-reactive histiocytes. This was associated with profound T-cell-dominated inflammation and severe neurodegeneration, characterized by a nearly complete loss of neurons and axons, and gliosis. (iii) Neurodegenerative lesions lacking infiltration of CD1a+ cells, mainly affecting the cerebellum and brainstem, exhibited a profound inflammatory process dominated by CD8-reactive lymphocytes, associated with tissue degeneration, microglial activation and gliosis. Patients with such lesions showed different stages of neurological deterioration. This study indicates that neurodegeneration in LCH occurs on the background of a T-cell-dominated inflammatory process and is characterized by neuronal and axonal destruction with secondary demyelination, resembling paraneoplastic encephalitis.
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PMID:Neuropathology of CNS disease in Langerhans cell histiocytosis. 1570 14


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