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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dendritic cells (DC) mediate airway Ag presentation and play key roles in asthma and infections. Although DC subsets are known to perform different functions, their occurrence in mouse lungs has not been clearly defined. In this study, three major lung DC populations have been found. Two of them are the myeloid and plasmacytoid DC (PDC) well-characterized in other lymphoid organs. The third and largest DC population is the integrin alpha(E) (CD103) beta(7)-positive and I-A(high)CD11c(high)-DC population. This population was found to reside in the lung mucosa and the vascular wall, express a wide variety of adhesion and costimulation molecules, endocytose avidly, present Ag efficiently, and produce IL-12. Integrin alpha(E)beta(7)(+) DC (alphaE-DC) were distinct from intraepithelial lymphocytes and distinguishable from CD11b(high) myeloid and mPDCA-1(+)B220(+)Gr-1(+) PDC populations in surface marker phenotype, cellular functions, and tissue localization. Importantly, this epithelial DC population expressed high levels of the Langerhans cell marker Langerin and the tight junction proteins Claudin-1, Claudin-7, and ZO-2. In mice with induced airway hyperresponsiveness and eosinophilia, alphaE-DC numbers were increased in lungs, and their costimulation and adhesion molecules were up-regulated. These studies show that alphaE-DC is a major and distinct lung DC population and a prime candidate APC with the requisite surface proteins for migrating across the airway epithelia for Ag and pathogen capture, transport, and presentation. They exhibit an activated phenotype in allergen-induced lung inflammation and may play significant roles in asthma pathogenesis.
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PMID:A major lung CD103 (alphaE)-beta7 integrin-positive epithelial dendritic cell population expressing Langerin and tight junction proteins. 1645 72

T cell activation is associated with a dramatic reorganization of cell surface proteins and associated signaling components into discrete subdomains within the immunological synapse in T cell:APC conjugates. However, the signals that direct the localization of these proteins and the functional significance of this organization have not been established. In this study, we have used wild-type and LFA-1-deficient, DO11.10 TCR transgenic T cells to examine the role of LFA-1 in the formation of the immunological synapse. We found that coengagement of LFA-1 is not required for the formation of the central supramolecular activation cluster (cSMAC) region, but does increase the accumulation of TCR/class II complexes within the cSMAC. In addition, LFA-1 is required for the recruitment and localization of talin into the peripheral supramolecular activation cluster region and exclusion of CD45 from the synapse. The ability of LFA-1 to increase the amount of TCR engaged during synapse formation and segregate the phosphatase, CD45, from the synapse suggests that LFA-1 might enhance proximal TCR signaling. To test this, we combined flow cytometry-based cell adhesion and calcium-signaling assays and found that coengagement of LFA-1 significantly increased the magnitude of the intracellular calcium response following Ag presentation. These data support the idea that in addition to its important role on regulating T cell:APC adhesion, coengagement of LFA-1 can enhance T cell signaling, and suggest that this may be accomplished in part through the organization of proteins within the immunological synapse.
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PMID:LFA-1-mediated T cell costimulation through increased localization of TCR/class II complexes to the central supramolecular activation cluster and exclusion of CD45 from the immunological synapse. 1764 Oct 28

We investigated Ag trafficking from the cornea and T effector cell activation in secondary lymphoid tissue after corneal transplantation. In preliminary experiments, the central cornea was shown to contain a population of CD45(+), CD11b(+), CD11c- cells, with a few MHC class II(+) cells, and F4/80(+) cells. However, MHC class II(+) passenger leukocytes in donor cornea after allografting did not traffic to the draining lymph node. Instead, Ag (plasmid) delivered to the eye via the donor cornea during allograft was detected in host CD11c(+) and F4/80(+) APC in the draining lymph nodes and spleen. The earliest detection of APC-associated Ag was at 6 h in the draining lymph node and 24 h in the spleen. After 48 h Ag was not detected in the draining lymph node but was still present in the spleen. Ag applied to the donor corneal epithelium before allografting induced Ag-specific T cell activation and expansion in the draining lymph node with a peak response at 4-6 days, indicating that cross-presentation of Ag had occurred. We conclude therefore, that Ag is transported from the donor cornea within host APC and that this event occurs within hours after grafting. Ag is cross-presented to host CD4(+) T cells on MHC class II and leads to the activation of Ag-specific effector T cells and clonal expansion in the draining lymph node.
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PMID:Cross presentation of antigen on MHC class II via the draining lymph node after corneal transplantation in mice. 1820 29

We retrospectively reviewed the flow cytometry (FCM) data from bone marrow aspirates of multiple myeloma (MM) patients before and after autologous stem cell transplantation (ASCT). Light scatter properties and CD38 expression were used to identify plasma cells, and CD19/CD45/CD56 further distinguished normal from abnormal plasma cells (NPC and APC, respectively), the latter defined as plasma cells with aberrant CD56, decreased or absent CD19 and/or CD45 expression. Forty-seven patients were screened. After ASCT, 66% (31/47) patients achieved complete remission (CR)/very good partial remission (VGPR), as compared to only 40% (19/47) prior to ASCT (P = 0.01). In 39 patients with data before and after ASCT, all 39 (100%) had a detectable APC population prior to ASCT. Twenty-six out of 39 patients (67%) also had detectable NPC. Following ASCT, the number of patients with detectable NPC increased to 35/39 (89%), while 3/39 (8%) had no detectable NPC and 1/39 (3%) had neither NPC nor APC. The proportion of APC decreased significantly after transplant from a median of 79% to 52% post-transplant (P < 0.001). The APC/total events ratio decreased significantly (P < 0.0001) after transplant. Prior to transplant, patients with less than 1.8% APC had significantly longer progression free survival (PFS) than patients with greater than 1.8% (P = 0.017, by log rank test), while the difference in overall survival did not achieve statistical significance (P = 0.081). Patients who achieved CR/VGPR after transplant had significantly longer PFS in comparison to all others (26 months vs. 11 months, P = 0.004). In conclusion, the detection of a significant population of APC by FCM prior to ASCT significantly correlates with poorer PFS in MM patients.
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PMID:Flow cytometric minimal residual disease monitoring in patients with multiple myeloma undergoing autologous stem cell transplantation: a retrospective study. 1823 1

Statistical mixture modeling provides an opportunity for automated identification and resolution of cell subtypes in flow cytometric data. The configuration of cells as represented by multiple markers simultaneously can be modeled arbitrarily well as a mixture of Gaussian distributions in the dimension of the number of markers. Cellular subtypes may be related to one or multiple components of such mixtures, and fitted mixture models can be evaluated in the full set of markers as an alternative, or adjunct, to traditional subjective gating methods that rely on choosing one or two dimensions. Four color flow data from human blood cells labeled with FITC-conjugated anti-CD3, PE-conjugated anti-CD8, PE-Cy5-conjugated anti-CD4, and APC-conjugated anti-CD19 Abs was acquired on a FACSCalibur. Cells from four murine cell lines, JAWS II, RAW 264.7, CTLL-2, and A20, were also stained with FITC-conjugated anti-CD11c, PE-conjugated anti-CD11b, PE-Cy5-conjugated anti-CD8a, and PE-Cy7-conjugated-CD45R/B220 Abs, respectively, and single color flow data were collected on an LSRII. The data were fitted with a mixture of multivariate Gaussians using standard Bayesian statistical approaches and Markov chain Monte Carlo computations. Statistical mixture models were able to identify and purify major cell subsets in human peripheral blood, using an automated process that can be generalized to an arbitrary number of markers. Validation against both traditional expert gating and synthetic mixtures of murine cell lines with known mixing proportions was also performed. This article describes the studies of statistical mixture modeling of flow cytometric data, and demonstrates their utility in examples with four-color flow data from human peripheral blood samples and synthetic mixtures of murine cell lines.
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PMID:Statistical mixture modeling for cell subtype identification in flow cytometry. 1849 51

The arrangement of molecules at the interface between T cells and APCs is known as the immunological synapse (IS). We conducted experiments with supported planar bilayers and transfected fibroblast APC to examine the IS formed by polarized Th1 and Th2 cells. Th1 cells formed typical "bull's-eye" IS with a ring of adhesion molecules surrounding MHC/TCR interactions at all Ag concentrations tested, while Th2 cells formed multifocal IS at high concentrations of Ag. At low Ag concentrations, the majority of Th2 cells formed IS with a compact, central accumulation of MHC/TCR, but ICAM-1 was not excluded from the center of the IS. Additionally, CD45 was excluded from the center of the interface between Th1 cells and APC, while CD45 was found at the center of the multifocal IS formed by Th2 cells. Finally, phosphorylated signaling molecules colocalized with MHC/TCR to a greater extent in Th2 IS. Together, our results indicate that the IS formed by Th1 and Th2 cells are distinct in structure, with Th2 cells failing to form bull's-eye IS.
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PMID:Th1 and Th2 cells form morphologically distinct immunological synapses. 1856 5

To study the prevalence of oral lesions in HIV infected patients and its relationship with CD4+ cell count in Georgia 732 HIV positive adult patients who were admitted to the Infectious Diseases, AIDS and Clinical Immunology Research Center (IDACIRC) since January, 2006 till October, 2008 were evaluated. Each patient underwent full clinical and standard laboratory examination. CD4+ cell count was determined by the Becton-Dickinson FACSCalibur flow cytometer (MultiTEST CD3 FITC/CD8 PE/CD45 PerCP/CD4 APC Reagent). Socio-demographic data was obtained using a standard questionnaire at the epidemiology department of IDACIRC. Oral manifestations were diagnosed according to EEC clearinghouse classification (1993). Oral lesions were revealed in 546 patients (75%). 186 patients (25%) did not exhibit any oral complications. The prevalence of two or more simultaneously exhibited types of lesions was as follows: three types of lesions were detected in 45 patients (6%) and two types of lesions were detected in 245 patients (33%). The investigation revealed oral candidiasis constituted the most common form of oral lesions, representing a 64% (467 patients), followed by HIV associated periodontal diseases in 216 patients (30%), recurrent aphthous like ulcerations in 118 patients (16%), oral hairy leukoplakia in 58 patients (8%), orolabial herpes simplex infection in 50 patients (7%), human papillomavirus (wart like lesions) in 37 patients (5%) and Kaposi's sarcoma in 3 patients (0.4%). Most of oral lesions cases were found in patients with low CD4+ cell count. Results of this study provide evidence that mucous membrane disorders with HIV infection might serve as an indicator for advanced HIV infection, immunosuppression and decreased CD4 cell counts. The physicians who are taking care of HIV patients have to be familiar with HIV-associated mucocutaneous diseases, their diagnoses, and management.
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PMID:Oral lesions in HIV-positive patients in Georgia. 1912 19

The diagnosis of classical Hodgkin lymphoma (CHL) has been made in tissue sections as attempts to identify neoplastic Hodgkin and Reed Sternberg (HRS) cells in lymph nodes by flow cytometry (FC) have been unsuccessful. However, we have recently demonstrated that HRS cells can be identified by FC, often present as T-cell-HRS-cell rosettes. In this study, we examined the usefulness of a novel 9-color (CD95-Pacific blue/CD64-fluorescein isothiocyanate/CD30-phycoerythrin [PE]/CD45-PE-Texas red/CD40-PE cyanine [Cy]5.5/CD20-PECy7/CD15-allophycocyanin [APC]/CD71-APC-AlexaFluor A700/CD5-APC-Cy7), single tube FC assay to diagnose CHL in lymph nodes. We used the FC assay to determine diagnostic sensitivity and specificity in 279 blindly identified and 141 selected (for specimen type or cytopreparation morphologic features suggesting CHL) tissues. Of the 53 morphologically defined CHL cases identified (10 in the unselected group; 43 in the selected group), the FC assay diagnostic sensitivity and specificity were 88.7% and 100%, respectively. With the current availability of 8 (or more) color clinical flow cytometers, this assay can now be applied to routinely immunophenotype and confirm a diagnosis of CHL or as an adjunct to immunohistochemical analysis.
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PMID:Flow cytometry can diagnose classical hodgkin lymphoma in lymph nodes with high sensitivity and specificity. 1922 36

In recent years, mesenchymal stem cells (MSC) have been attracting the greatest interest in the regeneration of injured tissues, autoimmune diseases, and transplantation of hematopoietic progenitor cells. Bone marrow (BM) represents the major source of MSC; however, umbilical cord blood (UCB) MSC has some advantages over BM, such as the higher differentiation capability and noninvasive collection methods. We sought to establish a 7-color, single-tube flow cytometric assay to quantify MSC in fresh tissues, namely BM and UCB, based on phenotypic markers of these cells. Moreover, we evaluated the differential expression of these markers in BM and UCB MSC. We used 5 UCB samples and 5 BM samples obtained from individuals without hematologic disease. To characterize MSC we used the following combination of monoclonal antibodies: CD71-FITC; CD105-PE; CD184-PE-Cy5; CD34-PE-Cy7; CD133-APC; CD45-APC-H7; CD44-Pacific blue, acquiring at least 1 million nucleated cells. We observed a greater number of BM MSC when compared with UCB MSC as well as some differences in the expression of some MSC antigens, particularly CD105 and CD44. Based on our preliminary results, phenotypic identification of MSC by flow cytometry is possible using a 7-color, single-tube assay. However, culture assays after sorting of cells characterized in this study are required to prove that they correspond to MSC.
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PMID:Quantification and immunophenotypic characterization of bone marrow and umbilical cord blood mesenchymal stem cells by multicolor flow cytometry. 1937 94

Satellite glial cells (SGC) in sensory ganglia tightly envelop the neuronal cell body to form discrete anatomical units. This type of glial cell is considered neuroectoderm-derived and provides physical support to neuron somata. There are scattered hints in the literature suggesting that SGC have an immune-related function within sensory ganglia. In this study, we addressed the hypothesis that SGC are tissue-resident APC. The immune phenotype and function of a large series (n = 40) of human trigeminal ganglia (TG) were assessed by detailed flow cytometry, in situ analyses, and functional in vitro assays. Human TG-resident SGC (TG-SGC) uniformly expressed the common leukocyte marker CD45, albeit at lower levels compared with infiltrating T cells, and the macrophage markers CD14, CD68, and CD11b. In addition, TG-SGC expressed the myeloid dendritic cell (DC) marker CD11c, the T cell costimulatory molecules CD40, CD54, CD80, and CD86 and MHC class II. However, the mature DC marker CD83 was absent on TG-SGC. Functionally, TG-SGC phagocytosed fluorescent bacteria, but were unable to induce an allogeneic MLR. Finally, TG-infiltrating T cells expressed the T cell inhibitory molecules CD94/NKG2A and PD-1, and the interacting TG-SGC expressed the cognate ligands HLA-E and PD-L1, respectively. In conclusion, the data demonstrate that human TG-SGC have a unique leukocyte phenotype, with features of both macrophages and immature myeloid DC, indicating that they have a role as TG-resident APC with potential T cell modulatory properties.
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PMID:Neuron-interacting satellite glial cells in human trigeminal ganglia have an APC phenotype. 1963 5


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