Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to investigate differences in T-B cell signalling between B cells from normal and immunodeficient mice. B cell blasts from normal and immunodeficient mice expressed comparable levels of membrane-associated IL-1. B cells from normal, but not immunodeficient mice, prefixed with glutaraldehyde and cultured with thymocytes or a T cell line BK33, induce in T cells production of a factor which causes release of IL-1 by macrophages. This factor, preincubated with B cells from immunodeficient mice significantly enhances their APC function. Furthermore, this cytokine induces expression of Lyb-5 alloantigen on B cells from immunodeficient mice. This effect could be blocked by neutralizing antibodies to IL-6 but not to IL-2, IL-4 or GM-CSF. We conclude that immature B cells from immunodeficient (CBA/N x BALB/c)F1 mice are unable to stimulate interacting T cells to produce IL-6 and therefore are inefficient antigen presenting cells.
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PMID:Presentation of antigen by B cell subsets. IV. Defective T-B cell signalling causes inability to present antigen by B cells from immunodeficient mice. 857 93

Peptide epitopes derived from differentiation antigens of the melanocyte lineage were recently identified in human melanomas as targets for MHC-restricted cytotoxic T lymphocytes (CTL). The characterization of multiple CTL-defined antigenic determinants has opened possibilities of development of antigen-targeted vaccines. In the present study, we determined CTL reactivity against melanoma-associated peptides derived from Melan A/MART-1, tyrosinase, and gp100/Pmel17 in 3 HLA-A2+ melanoma patients. Then, we assessed the immune responses to synthetic melanoma-associated peptides injected intradermally. After 3 cycles of immunization with peptide alone, we used systemic GM-CSF as an adjuvant during the fourth cycle of immunization. Enhanced DTH reactions and CD8+ CTL responses were observed after treatment with systemic GM-CSF. Immunohistochemical characterization of DTH-constituting elements revealed infiltrates of CD4+ and CD8+ T lymphocytes and strong expression of IL-2 and gammaIFN, suggesting the activation of CD4+ ThI and CD8+ CTL by peptides presented by MHC-class-I molecules of dermal APC. Objective tumor regression was documented in all patients. We conclude that systemic GM-CSF enhances immune responses to melanoma-associated peptides and supports CTL-mediated tumor rejection in vivo.
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PMID:Granulocyte-macrophage-colony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo. 869 May 25

The skin may be considered as well as a target and an iniator of self immune reactions. Two to 5% of the epidermal cells are Langerhans cells (LC) which are the only cells to specifically take, process and present the antigens to lymphocytes in order to induce an immune response. Such an ability and location of these cells enhance their role in antigenic stimulations and immuno-allergic reactions. TNF alpha was showed to potentiate the effect of GM-CSF for the generation of LC from their CD34+ precursors. Originated from the bone marrow, the LC colonize the epithelia where they act as antigen presenting cells by taking, processing antigens, and migrating to lymph nodes where they sensitize T cells. In vitro incubation of LC mimics their phenotypic, morphologic and functional maturation (enhanced accessory function) while they are migrating in vivo to lymph nodes where they are called interdigitating cells. Animal models might clarify such an hypothesis. Mechanisms leading to the LC immigration or the emigration from epithelia in order to play their immune functions remain obscure. Although LC are purified with difficulty and no immortalized human cell lines exist, these cells are still an ideal APC dendritic cell model. They will certainly be considered, in the next future, as the pivotal role of vaccinal strategy.
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PMID:[Recent data and current studies of epidermal Langerhans cells]. 878 88

We have investigated an improved method for generating sizable numbers of mature dendritic cells from nonproliferating progenitors in human blood. The procedure uses 1% human plasma in the place of 10% fetal calf serum and involves two steps. The first step or 'priming' phase is a 6-7 day culture of T cell depleted mononuclear cells in medium supplemented with GM-CSF and IL-4. The second step or 'differentiation' phase requires the exposure to macrophage conditioned medium. This medium cannot be replaced by several known cytokines such as TNF-alpha, IL-1, IL-6, IL-12 and IL-15, and cannot be inhibited with neutralizing antibodies to IL-1, TNF-alpha, IL-6 or IL-12 alone, or in combination. Using this two-step approach, we obtain substantial yields. About 1-3 x 10(6) mature dendritic cells are generated from 40 ml of blood vs. < 0.1 x 10(6) from noncytokine treated blood. The dendritic cells derive from progenitors found primarily in a radioresistant population of CD14+ and adherent blood mononuclear cells and have all the features of mature cells. They include a stellate cell shape, nonadherence to plastic, and very strong T cell stimulatory activity. Strong APC function was evident for both the proliferation of allogeneic T cells in the MLR, and the generation by syngeneic T cells of class I restricted, CTL responses to influenza virus. A panel of dendritic cell restricted markers is also expressed, including CD83, p55, and perinuclear CD68. All of these dendritic cell properties are retained for at least 3 days when the cytokines are removed, suggesting that these populations are stable and terminally differentiated. We suggest that these cells will be effective in vivo as adjuvants for active immunotherapy.
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PMID:Improved methods for the generation of dendritic cells from nonproliferating progenitors in human blood. 884 51

Dendritic cells (DC) are the most efficient APC for T cells. The clinical use of DC as vectors for anti-tumor and infectious disease immunotherapy has been limited by their trace levels and accessibility in normal tissue and terminal state of differentiation. In the present study, daily injection of human Flt3 ligand (Flt3L) into mice results in a dramatic numerical increase in cells co-expressing the characteristic DC markers-class II MHC, CD11c, DEC205, and CD86. In contrast, in mice treated with either GM-CSF, GM-CSF plus IL-4, c-kit ligand (c-kitL), or G-CSF, class II+ CD11c+ cells were not significantly increased. Five distinct DC subpopulations were identified in the spleen of Flt3L-treated mice using CD8 alpha and CD11b expression. These cells exhibited veiled and dendritic processes and were as efficient as rare, mature DC isolated from the spleens of untreated mice at presenting allo-Ag or soluble Ag to T cells, or in priming an Ag-specific T cell response in vivo. Dramatic numerical increases in DC were detected in the bone marrow, gastro-intestinal lymphoid tissue (GALT), liver, lymph nodes, lung, peripheral blood, peritoneal cavity, spleen, and thymus. These results suggest that Flt3L could be used to expand the numbers of functionally mature DC in vivo for use in clinical immunotherapy.
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PMID:Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified. 892 Aug 82

In this review, a sequential multiple-step model for T-cell activation is proposed. In a series of in vitro studies, highly purified freshly isolated human peripheral blood T lymphocytes were stimulated through the CD28 receptor, with mAb or with natural ligands B7-1 or B7-2, along with TCR stimulation, in the absence of other costimulatory interactions. Ligation of the CD28 receptor, along with stimulation of the TCR, was found to up-regulate pleiotropic in vitro activities, including the secretion of both Th1 and Th2-type cytokines, B-cell help, and the development of cytotoxic activity. This costimulatory action involves CD4+ and CD8+ as well as naive and memory T-cell subsets. The expression of B7-1 and B7-2 on professional APC in situ in both normal and pathological tissues, and its up-regulation on monocytes by GM-CSF and IFN-gamma is consistent with this role. Additional studies have addressed the contribution of interactions between CD28 and B7-1 and B7-2 in T-cell activation initiated by normal un-engineered APC, such as stimulation with recall antigens and primary MLR. Blockade of the interaction between CD28 and B7-1/B7-2 under these conditions failed to completely inhibit T-cell responses or to induce anergy. Complete inhibition and anergy were, however, induced with a combination of CsA, targeting downstream TCR-triggered signalling, as well as anti-B7-1- and anti-B7-2-directed reagents. Interestingly, and in contrast to anti-LFA-1 mAb, the addition of anti-B7-1 or anti-B7-2 reagents could be delayed until at least 48 h after the initiation of T-cell stimulation, indicating a requirement for a late interaction between CD28 and its counter-receptors. Interactions between CD40L on activated T cells and CD40 on APC may serve to sustain, enhance or prolong the presentation of B7-1 or B7-2 on the APC, and thus to prevent anergy induction, or ineffective or abortive T-cell stimulation. Based on these data a sequential multiple-step T-cell activation model is proposed, and novel strategies for immuno-intervention can be designed.
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PMID:CD80, CD86 and CD40 provide accessory signals in a multiple-step T-cell activation model. 901 Jul 19

A wide variety of human tumors express IL-10 for reasons poorly understood. We have analyzed the effect of spontaneous IL-10 expression by a mouse tumor (J558L) on its immunoparalyzing effect. Because "cross-priming" of T cells by host Ag-presenting cells for MHC class I-restricted tumor Ags is a major pathway for induction of tumor immunity and that is enhanced by granulocyte-macrophage (GM) CSF, we expressed this cytokine in J558L cells. GM-CSF-secreting cells were not effective when used for immunization against challenge with the parental tumor. Inhibition of IL-10 expression through an IL-10 antisense retrovirus restored the vaccine efficacy of GM-CSF-producing J558L cells, demonstrating a direct role of IL-10 in paralyzing the GM-CSF-induced antitumor immune response. Since the tumor used for challenge produced IL-10, we conclude that IL-10 interfered primarily with the initiation but not the effector phase of the immune response. Immunohistochemical analysis of the vaccine site showed a GM-CSF-induced accumulation of dendritic cells (DC) (MHC class II+ and DEC-205+) in the absence of IL-10. In the presence of IL-10, DC accumulation was completely inhibited. Together, our results demonstrate an antagonistic effect of IL-10 with respect to GM-CSF-induced DC accumulation and tumor immunity and suggest a new mechanism by which tumors escape immune recognition: namely by preventing APC from obtaining access to tumor Ags.
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PMID:Interleukin-10 prevents dendritic cell accumulation and vaccination with granulocyte-macrophage colony-stimulating factor gene-modified tumor cells. 921 94

The study of liver dendritic cells (DC) and their progenitors is restricted by the small numbers that can be isolated or propagated from normal hepatic tissue. We examined the ex vivo growth, phenotype, and function of these cells after the administration to mice of the recently cloned hemopoietic growth factor flt3 ligand (FL), which is highly effective in mobilizing stem/progenitor cells. FL treatment (10 microg/day for 10 days) resulted in a mean 14-fold increase in the absolute number of nonparenchymal cells recovered from collagenase-digested livers compared with the control value. Culture of these nonparenchymal cells in granulocyte-macrophage CSF (GM-CSF; 1000 U/ml) resulted in the early formation of proliferating cell clusters and maximal release (within 4-5 days) of markedly increased numbers of nonadherent, low buoyant density cells per liver. Maximal release of low buoyant density cells propagated from control livers was at the later time of 6 to 8 days. Cells from both sources were DEC-205+, CD11c+, MHC class II+, CD80(low) (i.e., low level of CD80), CD86(low) and CD40(low). This immature phenotype was linked to poor T cell allostimulatory activity, indicative of DC progenitors. Propagation of cells from livers of FL-treated mice in GM-CSF and IL-4 resulted in a more mature DC phenotype and function. Maturational changes were also observed following exposure of the GM-CSF-stimulated progenitors to type 1 collagen for 3 additional days. The ability of FL to boost production of large numbers of liver DC progenitors provides opportunities for the further study of these important APC in normal liver immunobiology and in immune-mediated hepatic disorders.
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PMID:In vivo administration of flt3 ligand markedly stimulates generation of dendritic cell progenitors from mouse liver. 937 22

Human peripheral blood monocytes activated by GM-CSF plus IL-4 have recently been found to exhibit characteristics of putative dendritic cells (DC). These cytokine-activated monocytes (CAM) may express novel activation Ag that contribute significantly to their antigen presentation potency. To examine that possibility, mAb specific for CAM were derived. Seven mAb that stained CAM but not unactivated monocytes and other peripheral blood mononuclear cell types were identified. Further screening with a panel of cell lines identified two CAM-specific mAb. The first mAb, 2.1D10, was found to be mannose-receptor specific. A second mAb, 6.3B7, immunoprecipitated a 190-kDa Ag. It stained neither activated B cells nor the putative peripheral blood precursor DC population. Furthermore, 6.3B7 did not recognize determinants in asparagine-linked carbohydrate chains or in sialic acid-containing structures. These mAb against CAM membrane proteins may provide new insights into the requirements for optimal antigen presentation by macrophages and other APC types.
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PMID:Monoclonal antibodies against human dendritic cell-like peripheral blood monocytes activated by granulocyte/macrophage-colony-stimulating factor plus interleukin 4. 951 3

The CTL response to HIV-I can be vigorous, but antigen presenting cell requirements have not been studied in detail. To approach this question, we have examined the dendritic cell populations that can be obtained from the blood of HIV-1 infected individuals. We studied 13 asymptomatic patients, who spanned a wide range of plasma viremia and CD4 counts. We show here that sizeable numbers of mature dendritic cells can be generated from nonproliferating progenitors in the blood of HIV + patients using a recently developed approach. The procedure involves two steps. The first step or 'priming' phase is a 7 day culture of T-cell depleted mononuclear cells in medium supplemented with GM-CSF and IL-4. The second step or 'differentiation' phase requires the exposure to monocyte conditioned medium. The yields of DCs from HIV + individuals were comparable to normal blood donors, 0.4 - 3 x 10(6) mature dendritic cells from 50 ml of blood. Strong APC function was evident for both the proliferation of allogeneic T-cells in the MLR, and the generation by syngeneic T-cells of class I restricted, CTL responses to influenza virus. A panel of dendritic cell restricted markers are expressed, including CD83, p55, and perinuclear CD68. By semi-quantitative PCR analysis, the cytokine derived cells did not express HIV-1 DNA. We suggest that these blood derived dendritic cells will be effective for studies of immune responses to HIV-1 antigens and may be considered as adjuvants for active immunotherapy.
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PMID:Dendritic cells generated from blood monocytes of HIV-1 patients are not infected and act as competent antigen presenting cells eliciting potent T-cell responses. 1020 44


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