Chang SK et al. (JUN 2008)
Journal of immunology (Baltimore,Md. : 1950) 180 11 7394--403
B lymphocyte stimulator regulates adaptive immune responses by directly promoting dendritic cell maturation.
B lymphocyte stimulator (BLyS) is a well-known direct costimulator of adaptive immune cells,particularly B lineage cells. However,we have reported recently that BLyS is also able to activate monocytes. Other innate immune cells,such as dendritic cells (DCs),play a key role in the initiation of adaptive immune responses and the purpose of the current study was to assess whether there is a direct role for BLyS in modulating human DC functions. In this study,we show that BLyS induces DC activation and maturation. Thus,BLyS strongly induced up-regulation of surface costimulatory molecule expression and secretion of specific cytokines and chemokines in DCs. BLyS-stimulated DCs (BLyS-DCs) were also able to augment allogeneic CD4 T cell proliferation to a greater extent than control DCs. BLyS-DCs secreted elevated levels of the major Th1-polarizing cytokine,IL-12p70,and they promoted naive CD4 T cell differentiation into Th1 T cells. Regarding BLyS receptor expression,DCs primarily express cytoplasmic transmembrane activator and CAML interactor; however,low levels of cell surface transmembrane activator and CAML interactor are expressed as well. Collectively,our data suggest that BLyS may modulate adaptive immune cells indirectly by inducing DC maturation.
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产品类型：
产品号#：
19155
19155RF
21000
20119
20155
产品名：
RoboSep™- S
RoboSep™ 吸头组件抛光剂
RoboSep™分选管套装（9个塑料管）
Addo MM et al. (FEB 2003)
Journal of virology 77 3 2081--92
Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load.
Cellular immune responses play a critical role in the control of human immunodeficiency virus type 1 (HIV-1); however,the breadth of these responses at the single-epitope level has not been comprehensively assessed. We therefore screened peripheral blood mononuclear cells (PBMC) from 57 individuals at different stages of HIV-1 infection for virus-specific T-cell responses using a matrix of 504 overlapping peptides spanning all expressed HIV-1 proteins in a gamma interferon-enzyme-linked immunospot (Elispot) assay. HIV-1-specific T-cell responses were detectable in all study subjects,with a median of 14 individual epitopic regions targeted per person (range,2 to 42),and all 14 HIV-1 protein subunits were recognized. HIV-1 p24-Gag and Nef contained the highest epitope density and were also the most frequently recognized HIV-1 proteins. The total magnitude of the HIV-1-specific response ranged from 280 to 25,860 spot-forming cells (SFC)/10(6) PBMC (median,4,245) among all study participants. However,the number of epitopic regions targeted,the protein subunits recognized,and the total magnitude of HIV-1-specific responses varied significantly among the tested individuals,with the strongest and broadest responses detectable in individuals with untreated chronic HIV-1 infection. Neither the breadth nor the magnitude of the total HIV-1-specific CD8+-T-cell responses correlated with plasma viral load. We conclude that a peptide matrix-based Elispot assay allows for rapid,sensitive,specific,and efficient assessment of cellular immune responses directed against the entire expressed HIV-1 genome. These data also suggest that the impact of T-cell responses on control of viral replication cannot be explained by the mere quantification of the magnitude and breadth of the CD8+-T-cell response,even if a comprehensive pan-genome screening approach is applied.
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产品类型：
产品号#：
15022
15062
15023
15063
产品名：
RosetteSep™人CD4+ T细胞富集抗体混合物
RosetteSep™人CD4+ T细胞富集抗体混合物
RosetteSep™人CD8+ T细胞富集抗体混合物
RosetteSep™人CD8+ T细胞富集抗体混合物
Fogli M et al. (JUL 2008)
PLoS pathogens 4 7 e1000101
Lysis of endogenously infected CD4+ T cell blasts by rIL-2 activated autologous natural killer cells from HIV-infected viremic individuals.
Understanding the cellular mechanisms that ensure an appropriate innate immune response against viral pathogens is an important challenge of biomedical research. In vitro studies have shown that natural killer (NK) cells purified from healthy donors can kill heterologous cell lines or autologous CD4+ T cell blasts exogenously infected with several strains of HIV-1. However,it is not known whether the deleterious effects of high HIV-1 viremia interferes with the NK cell-mediated cytolysis of autologous,endogenously HIV-1-infected CD4+ T cells. Here,we stimulate primary CD4+ T cells,purified ex vivo from HIV-1-infected viremic patients,with PHA and rIL2 (with or without rIL-7). This experimental procedure allows for the significant expansion and isolation of endogenously infected CD4+ T cell blasts detected by intracellular staining of p24 HIV-1 core antigen. We show that,subsequent to the selective down-modulation of MHC class-I (MHC-I) molecules,HIV-1-infected p24(pos) blasts become partially susceptible to lysis by rIL-2-activated NK cells,while uninfected p24(neg) blasts are spared from killing. This NK cell-mediated killing occurs mainly through the NKG2D activation pathway. However,the degree of NK cell cytolytic activity against autologous,endogenously HIV-1-infected CD4+ T cell blasts that down-modulate HLA-A and -B alleles and against heterologous MHC-I(neg) cell lines is particularly low. This phenomenon is associated with the defective surface expression and engagement of natural cytotoxicity receptors (NCRs) and with the high frequency of the anergic CD56(neg)/CD16(pos) subsets of highly dysfunctional NK cells from HIV-1-infected viremic patients. Collectively,our data demonstrate that the chronic viral replication of HIV-1 in infected individuals results in several phenotypic and functional aberrancies that interfere with the NK cell-mediated killing of autologous p24(pos) blasts derived from primary T cells.
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产品类型：
产品号#：
19052
19052RF
19055
19055RF
产品名：
EasySep™人CD4+ T细胞富集试剂盒
RoboSep™ 人CD4+ T细胞富集试剂盒含滤芯吸头
EasySep™人NK细胞富集试剂盒
RoboSep™ 人NK细胞富集试剂盒含滤芯吸头
Kourjian G et al. (MAY 2016)
Journal of Immunology 196 9 3595--607
HIV Protease Inhibitor-Induced Cathepsin Modulation Alters Antigen Processing and Cross-Presentation.
Immune recognition by T cells relies on the presentation of pathogen-derived peptides by infected cells,but the persistence of chronic infections calls for new approaches to modulate immune recognition. Ag cross-presentation,the process by which pathogen Ags are internalized,degraded,and presented by MHC class I,is crucial to prime CD8 T cell responses. The original degradation of Ags is performed by pH-dependent endolysosomal cathepsins. In this article,we show that HIV protease inhibitors (PIs) prescribed to HIV-infected persons variably modulate cathepsin activities in human APCs,dendritic cells and macrophages,and CD4 T cells,three cell subsets infected by HIV. Two HIV PIs acted in two complementary ways on cathepsin hydrolytic activities: directly on cathepsins and indirectly on their regulators by inhibiting Akt kinase activities,reducing NADPH oxidase 2 activation,and lowering phagolysosomal reactive oxygen species production and pH,which led to enhanced cathepsin activities. HIV PIs modified endolysosomal degradation and epitope production of proteins from HIV and other pathogens in a sequence-dependent manner. They altered cross-presentation of Ags by dendritic cells to epitope-specific T cells and T cell-mediated killing. HIV PI-induced modulation of Ag processing partly changed the MHC self-peptidome displayed by primary human cells. This first identification,to our knowledge,of prescription drugs modifying the regulation of cathepsin activities and the MHC-peptidome may provide an alternate therapeutic approach to modulate immune recognition in immune disease beyond HIV.
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EasySep™小鼠TIL（CD45）正选试剂盒
EasySep™非人灵长类T细胞分选试剂盒 通过免疫磁珠负选从包括恒河猴在内的非人灵长类中分离出无磁珠标记的T细胞
EasySep™非人灵长类CD4+ T细胞分选试剂盒
EasySep™非人灵长类CD8+ T细胞分选试剂盒
产品手册EasySep™ Direct 仅需20分钟，从全血中分选细胞
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