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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study antitumor functions of T-lymphocyte subpopulations in the blood [peripheral blood lymphocytes (PBLs)] and tumor-draining lymph nodes (LNs) of patients (n = 26) with squamous cell carcinoma of the head and neck (SCCHN), antibody-coated devices were used to positively select CD8+ or CD4+ cells. The mean percentage of CD8+ cells captured on antibody-coated flasks from PBLs was 92% and that captured from lymph node lymphocytes (LNLs) was 98%. The initial enrichment in CD4+ T-cells was comparable. CD8+ T-lymphocytes captured from PBLs proliferated as well as unseparated lymphocytes in both patients with SCCHN and normal donors, while captured CD4+ PBLs of the patients showed significantly lower expansion than those of normal volunteers. Unseparated LNLs proliferated as well as PBLs, but captured CD4+ or CD8+ LNLs failed to proliferate in the presence of interleukin 2 (100 units/ml) and phytohemagglutinin (5 micrograms/ml). The addition to captured LNL cultures of irradiated autologous or allogeneic feeder cells significantly improved expansion of CD8+ LNLs but not CD4+ LNLs. During 15-day culture of captured CD8+ PBLs or CD8+ LNLs in the presence of feeder cells, a significant (P less than 0.05) enrichment in CD8+ T-cells was maintained [94 +/- 5% (mean +/- SEM) or 99.5 +/- 0.1%, respectively, on day 15]. Capture of CD8+ LNLs and their expansion resulted in the outgrowth of CD8+CD11b- effectors which had no or little cytotoxicity against Daudi, low cytotoxicity against K562, and very high levels of cytotoxicity against 4 different natural killer cell-resistant SCCHN targets, as measured in 4-h 51Cr release assays. Such significant enrichment in SCCHN-restricted cytotoxicity could be obtained with LNLs from tumor-uninvolved LNs but not from tumor-involved LNs. Captured and cultured CD4+ LNLs had no preferential anti-SCCHN cytotoxicity. The addition of irradiated autologous tumor cells to captured CD8+ PBLs did not result in improved proliferation or antitumor function of the effector cells. Positive selection on antibody-coated flasks of CD8+ T-lymphocytes from tumor-uninvolved LNs of patients with SCCHN led to the enrichment in SCCHN-restricted but the major histocompatibility complex-unrestricted effector cells in 15-day cultures. Thus, CD8+ lymphocytes separated from tumor-draining LNs in patients with head and neck cancer contained cytolytic T-cell precursors capable of developing into effectors with preferential activity against SCCHN targets.
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PMID:Enrichment in tumor-reactive CD8+ T-lymphocytes by positive selection from the blood and lymph nodes of patients with head and neck cancer. 167 10

Cutaneous T-cell lymphoma is characterized by infiltration of the skin by activated CD4+ T lymphocytes. The mechanism by which these T lymphocytes achieve and maintain their activated state is unknown. Antigen-specific activation of T lymphocytes is dependent upon antigen-presenting cells which express HLA-DR class II major histocompatibility complex molecules, such as epidermal Langerhans cells. In addition to CD1+DR+ Langerhans cells, cutaneous T-cell lymphoma lesional epidermis contains major histocompatibility complex class II positive non-Langerhans cell populations, including CD1+OKM5+ bone-marrow-derived cells and DR+ keratinocytes. We asked whether any of these epidermal cell populations demonstrate capacity to activate T lymphocytes. Various numbers of epidermal cells from uninvolved and involved cutaneous T-cell lymphoma plaques were therefore used to stimulate autologous CD4+ and CD8+ T lymphocytes in the absence of exogenous antigen. Involved epidermal cells potently induced proliferation of CD4+ T lymphocytes (S.I. +/- SEM = 466 +/- 45). In contrast, uninvolved epidermal cells only induced background levels of proliferation (S.I. +/- SEM = 2 +/- 0.5, N = 8, p less than 0.01). Neither involved nor uninvolved epidermal cells were able directly to activate CD8+ lymphocytes. The capability of involved epidermal cells to activate CD4+ T lymphocytes was dependent upon CD1+DR+ leukocytes and not DR+ keratinocytes, because depletion of either HLA-DR+, CD1+ or HLe1+ epidermal cells totally abrogated the T-lymphocyte proliferation. Interestingly, on a cell per cell basis CD1+DR+ cells obtained from involved skin, demonstrated relative to CD1+DR+ cells from uninvolved skin, enhanced capacity to activate CD4+ T lymphocytes. Furthermore, CD1+OKM5+ cells from involved epidermis stimulated autologous CD4+ T lymphocytes. This indicates that a unique hitherto undescribed CD1+OKM5+ epidermal antigen-presenting cell population may participate in T-lymphocyte activation. These findings provide support for the concept that the epidermal cells in cutaneous T-cell lymphoma patients, particularly the antigen-presenting cells, may contribute significantly to the activation of CD4+ malignant and/or non-malignant inflammatory T lymphocytes within the skin.
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PMID:Cutaneous T-cell lymphoma lesional epidermal cells activate autologous CD4+ T lymphocytes: involvement of both CD1+OKM5+ and CD1+OKM5- antigen-presenting cells. 196 33

The surface expression of intercellular adhesion molecule 1 (ICAM-1) and class I and class II major histocompatibility complex molecules on cultured dermal fibroblasts from 7 scleroderma patients and 6 control donors was compared. Scleroderma fibroblast lines contained 41.0 +/- 3.0% (mean +/- SEM) cells with high levels of ICAM-1 expression (ICAM-1-high), whereas 26.9 +/- 1.5% of control fibroblasts were ICAM-1-high (P = 0.0003). There were no differences in the expression of class I and class II molecules. ICAM-1-high and ICAM-1-low fibroblasts produced equal amounts of total protein and procollagen. The increase in the number of ICAM-1-high fibroblasts in scleroderma patients may facilitate T cell activation and lymphokine production, and thus indirectly contribute to the fibrotic process.
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PMID:Increased expression of intercellular adhesion molecule 1 on the fibroblasts of scleroderma patients. 197 37

Using human thymocytes and autologous thymic epithelial (TE) cells grown in vitro in long-term culture, we have found TE cells can function as accessory cells for mitogen-induced mature thymocyte activation. Tritiated thymidine incorporation, blast formation, and protein synthesis were all induced in accessory cell-depleted thymocytes by autologous TE cells in the presence of suboptimal concentrations of PHA. After 3 days of mitogen stimulation of thymocyte-TE cell cocultures in vitro, thymocyte blasts bound to TE cells and 77 +/- 4% (mean +/- SEM) of TE cells acquired expression of major histocompatibility complex (MHC) class II (DR) antigen. TE accessory cell function for thymocyte activation was dependent on the number of TE cells added to thymocyte cultures, was not dependent on TE cell division, but did require TE cell protein synthesis. In thymocyte separation experiments, the predominant cell type responding to PHA in the presence of TE cells was T6- mature (stage III) thymocytes. Thus, human TE cells are capable of providing signals that lead to mature thymocyte activation.
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PMID:Human thymic epithelial cells function as accessory cells for autologous mature thymocyte activation. 349 29

Assays were developed to detect cell-mediated immune destruction of pancreatic islet beta cells by lymphoid cells isolated from diabetic BioBreeding/Worcester (BB/W) rats. Splenic lymphoid cells from diabetic (D), diabetes-prone (DP), and diabetes-resistant (DR) BB/W rats were incubated for 2 days with monolayer cultures of major histocompatibility complex (MHC)-compatible Wistar-Furth (WF) rat islet cells or a rat islet cell line (RIN), and islet beta cell survival was determined by measuring insulin content in the cultures. D splenic lymphoid cells significantly decreased insulin content in WF rat islet (-32%) and RIN cultures (-77%). DP cells also significantly reduced the insulin content in WF rat islet (-20%) and RIN cultures (-63%), whereas DR cells had no significant effect. Islet-directed cytotoxicity was detected also by the release of 51Cr from RIN cells incubated for 8 h with BB/W spleen cells. Cytotoxicity was linearly related to the number of effector spleen cells. At a target: effector of 1:20, lysis (mean +/- SEM) of RIN target cells by spleen cells from D rats (21.6 +/- 2.0%) and DP rats (16.5 +/- 4.1%) was significantly greater than the effect of DR spleen cells (5.4 +/- 1.0%). D and DP splenic lymphoid cells activated in vitro for 2 days with concanavalin A exhibited a doubling of cytotoxicity to RIN islet cells. These results provide direct evidence for lymphoid cell-mediated immune damage to islet beta cells in diabetic BB rats.
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PMID:Lymphoid cells of BB/W diabetic rats are cytotoxic to islet beta cells in vitro. 389 76

Virus-specific cytotoxic T lymphocytes (CTLs) have been suggested to be responsible for the liver injuries in patients with hepatitis C virus (HCV) infection. However, there has been no report of direct evidence to substantiate this hypothesis. In this study, we performed in vitro autologous hepatocytotoxicity assay in 45 patients to examine a possible role of CTLs to HCV-infected live cells. The data were correlated with histology activity index of liver biopsy specimens. Lymphocyte subsets and hepatocyte expression of human major histocompatibility complex antigens class I and class II (HLA-I and HLA-II) were also evaluated. The immunohistochemical study showed more prominent HLA-I expression than HLA-II on hepatocytes (mean score +/- SEM:2.34 +/- 0.11 vs. 0.42 +/- 0.08; P < .01). The lymphocyte subset analysis showed that CD8+ T cells were dominant in the lobular areas showing spotty necrosis, whereas CD4+ T cells were prominent in the portal and periportal areas (P < .01). Most patients had a significant T cell-mediated cytotoxicity to hepatocytes as compared with non-T cells (percentage cytotoxicity +/- SEM:46.4 +/- 2.3 vs. 13.8 +/- 2.7; P < .001). T cell-mediated hepatocytotoxicity had a linear correlation with HAI (P < .05). The T cell-mediated cytotoxicity could be blocked by anti-CD8 (43.7% vs. 18.5%, P < .05) but not by anti-CD4 or anti-HLA-II monoclonal antibodies. These findings strongly suggest that HLA-I-restricted, CD8+ T cell-mediated hepatocytotoxicity is an important pathogenetic mechanism in patients with chronic HCV infection.
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PMID:T-cell--mediated autologous hepatocytotoxicity in patients with chronic hepatitis C virus infection. 759 Jun 49

Human lung dendritic cells (DC) are considerably more potent than alveolar macrophages (AM) in inducing allogeneic T-cell proliferation. Tumor necrosis factor (TNF) alpha and beta produced during alloreaction are likely to be major inflammatory cytokines involved. Their concentrations were therefore analyzed during the interaction of AM or DC with allogeneic T cells. TNF alpha and TNF beta levels were respectively three-fold and sevenfold higher in the presence of DC as compared with AM. Cytokines such as interleukin-4 (IL-4), interleukin-10 (IL-10), and transforming growth factor beta (TGF beta) were compared as to their ability to control DC-induced T-cell proliferation as well as TNF alpha or TNF beta production. IL-10 had the unique capacity of reducing both TNF alpha and TNF beta production by 60 +/- 5% (mean +/- SEM) and 63 +/- 12%, respectively, while inhibiting T-cell proliferation by only 32 +/- 23%. IL-4 and TGF beta increased the release of TNF beta by 275 +/- 22% and 95 +/- 32%, respectively, while that of TNF alpha was slightly decreased or unchanged. An additive effect of IL-10 to cyclosporine was found for all three parameters studied. Interaction between CD4 or CD8 with DC was affected similarly by IL-10. Part of this effect could be due to the downregulation of class I and class II major histocompatibility complex expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-10 decreases tumor necrosis factor alpha and beta in alloreactions induced by human lung dendritic cells and macrophages. 759 41

Macrophage major histocompatibility complex (MHC) class II antigen expression is associated with defective antigen presentation to T lymphocytes in animals and is predictive of patient outcome after major trauma or sepsis. In this study, class II antigen (HLA-DR and DQ) expression on peripheral blood monocytes was investigated in patients with inflammatory bowel disease in relation to disease activity and outcome. The percentage positivity and fluorescent intensity of expression of HLA-DR and DQ antigens on monocytes were determined in whole blood samples using dual colour immunofluorescence labelling and flow cytometry. Disease activity was assessed using clinical and laboratory indices. There was no significant difference in percentage positivity or fluorescent intensity of class II antigen expression between patients with Crohn's disease, those with ulcerative colitis, and healthy volunteers. The percentage of monocytes displaying HLA-DR positivity was significantly decreased in patients with active ulcerative colitis (active %: 49.5 (5.6); inactive %: 78.9 (6.9); p = 0.01). Data expressed as mean (SEM). In patients requiring surgical resection of diseased bowel, the percentage of monocytes displaying HLA-DR positivity (51.9 (4.0) %) was significantly reduced compared with patients receiving medical treatment alone (81.1 (3.5) %; p < 0.001). Reduced monocyte HLA-DR expression is therefore associated with disease activity and seems to predict outcome in patients with inflammatory bowel disease.
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PMID:Class II major histocompatibility complex antigen expression on peripheral blood monocytes in patients with inflammatory bowel disease. 817 90

Tumor infiltrating lymphocytes (TIL) were cultured from 17 B-cell lymphoma specimens derived from patients with predominantly low-grade malignancies. Specimens included 15 lymph-node biopsies, 1 malignant pleural effusion, and PBL from 1 patient with circulating lymphoma cells. The phenotypic and proliferative characteristics of TIL cultured in interleukin-2 (IL-2) were studied, as well as cytolysis and cytokine secretion in response to autologous tumor. Flow cytometry of fresh tumor suspensions showed that 50% of cells (median) were malignant B cells and 36% were infiltrating T lymphocytes. After culture for approximately 1 month, TIL were 75% +/- 8% CD3+ (mean +/- SEM), 47% +/- 8% CD4+ and 35% +/- 7% CD8+. TIL proliferation was modest in most cases: the median maximum expansion was 32-fold in 25 days. Lysis of autologous tumor in 4-hour 51Cr release assays was mediated by 2 of 12 TIL studied, but was nonspecific. However, these same two TIL, when cocultured with various tumor stimulators, preferentially secreted tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor after autologous tumor stimulation; unstimulated TIL secreted undetectable or barely detectable levels of these cytokines. In one TIL culture, cytokines were secreted by purified CD4+ TIL but not by CD8+ cells, and secretion was completely abrogated by the anti-major histocompatibility complex (MHC) class II antibody IVA12. Thus, although specific cytokine secretion by lymphoma TIL in response to autologous tumor was observed, it occurred in fewer than 20% of patients studied.
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PMID:Tumor-infiltrating lymphocytes derived from select B-cell lymphomas secrete granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha in response to autologous tumor stimulation. 835 84

Transgene expression in the brain of St. Kitts green monkey, Cercopithecus aethiops sabeus, was studied following injection of a serotype 5 adenoviral vector deleted in E1 and E3. The vector harbored the transgene for Escherichia coli beta-galactosidase (beta-Gal) with the simian virus 40 (SV40) nuclear localization signal under control of the Rous sarcoma viral (RSV) long terminal repeat. Several titers ranging from 5 x 10(7) to 2 x 10(9) plaque-forming units (PFU) in volumes ranging from 5 to 250 microl were injected into the caudate nuclei of 18 monkeys. Monkeys were treated with dexamethasone for 9 days, beginning the day prior to surgery, and were sacrificed at 1 week or at 1, 2, or 3 months. At 1 week, beta-Gal was expressed in thousands of cells, including both neurons and astrocytes. In addition, some dopaminergic neurons in the substantia nigra expressed transgene, suggesting retrograde transport of the vector. At 1 month 162,000+/-68,000 (SEM) or 65,000+/-29,000 beta-Gal-expressing cells persisted in striatum injected with 6 x 10(8) PFU in 30 microl or 5 x 10(7) PFU in 5 microl, respectively. Transgene expression was also observed in one of two monkeys sacrificed at 2 months and in a single monkey sacrificed at 3 months. No transgene expression was observed at 1 month in striatum injected with a higher titer (2 x 10(9) PFU in 100 microl) or more dilute vector (5 x 10(7) PFU in 30 microl). Staining for the major histocompatibility complex II (MHC II) subtype DR showed intense staining in sites injected with a higher vector titer, in which no transgene persisted at 1 month, whereas low to moderate staining was present in sites with high transgene expression. These observations suggest that there is an optimal range of vector titers for obtaining persistent transgene expression from E1E3-deleted adenovirus in primate brain, above which host responses limit transgene stability.
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PMID:Adenovirus-mediated transgene expression in nonhuman primate brain. 1034 May 49


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