abstract：:Microbial DNA sequences containing unmethylated CpG dinucleotides activate Toll-like receptor 9 (TLR9). We have found that TLR9 is localized to the endoplasmic reticulum (ER) of dendritic cells (DCs) and macrophages. Because there is no precedent for immune receptor signaling in the ER, we investigated how TLR9 is act...

journal_title：Nature immunology

authors： Latz E,Schoenemeyer A,Visintin A,Fitzgerald KA,Monks BG,Knetter CF,Lien E,Nilsen NJ,Espevik T,Golenbock DT

更新日期：2004-02-01 00:00:00

abstract：:Tumor necrosis factor receptor 1 (TNFR1)-associated death domain protein (TRADD) is essential in recruiting signaling molecules to the TNFR1 receptor complex. Interferon-gamma (IFN-gamma) is a potent activator of macrophages and uses signal transducer and activator of transcription 1-alpha (STAT1-alpha) for signal tra...

journal_title：Nature immunology

authors： Wesemann DR,Qin H,Kokorina N,Benveniste EN

更新日期：2004-02-01 00:00:00

abstract：:Gadd45beta (growth arrest and DNA damage-inducible, beta) is involved in cell cycle arrest, apoptosis, signal transduction and cell survival. In T cells, Gadd45b was rapidly induced by T cell receptor (TCR) and inflammatory signals. Deficiency of Gadd45beta in CD4+ T cells impaired their responses to TCR stimulation o...

journal_title：Nature immunology

authors： Lu B,Ferrandino AF,Flavell RA

更新日期：2004-01-01 00:00:00

abstract：:The active ubiquitin E3 ligase GRAIL is crucial in the induction of CD4 T cell anergy. Here we show that GRAIL is associated with and regulated by two isoforms of the ubiquitin-specific protease otubain 1. In lethally irradiated mice reconstituted with bone marrow cells from T cell receptor-transgenic mice retrovirall...

journal_title：Nature immunology

authors： Soares L,Seroogy C,Skrenta H,Anandasabapathy N,Lovelace P,Chung CD,Engleman E,Fathman CG

更新日期：2004-01-01 00:00:00

abstract：:Caspases are important for apoptosis but are also involved in mammalian cell survival and cell division. Here we report that caspase-3 is a negative regulator of B cell cycling. Mice deficient in caspase-3 (Casp3-/- mice) have increased numbers of splenic B cells that show normal apoptosis but enhanced proliferation i...

journal_title：Nature immunology

authors： Woo M,Hakem R,Furlonger C,Hakem A,Duncan GS,Sasaki T,Bouchard D,Lu L,Wu GE,Paige CJ,Mak TW

更新日期：2003-10-01 00:00:00

abstract：:The pre-B cell receptor (preBCR), composed of mu immunoglobulin (Ig) and surrogate light chains, signals large 'preB-II' cells to proliferate in the apparent absence of ligands or cooperating cells. We deleted the N-terminal, nonimmunoglobulin (nonlg) portion of lambda5, or mutated seven arginine residues in it to ser...

journal_title：Nature immunology

authors： Ohnishi K,Melchers F

更新日期：2003-09-01 00:00:00

abstract：:Using a human CD25 reporter transgene controlled by regulatory sequences from the gene encoding pre-T cell receptor alpha, we identified a common lymphocyte precursor (CLP-2) population that, in contrast to the previously identified CLP-1 population, was c-Kit-B220+. In short-term culture, the CLP-2 could be derived f...

journal_title：Nature immunology

authors： Martin CH,Aifantis I,Scimone ML,von Andrian UH,Reizis B,von Boehmer H,Gounari F

更新日期：2003-09-01 00:00:00

abstract：:The extracellular protein Spätzle is required for activation of the Toll signaling pathway in the embryonic development and innate immune defense of Drosophila. Spätzle is synthesized as a pro-protein and is processed to a functional form by a serine protease. We show here that the mature form of Spätzle triggers a To...

journal_title：Nature immunology

authors： Weber AN,Tauszig-Delamasure S,Hoffmann JA,Lelièvre E,Gascan H,Ray KP,Morse MA,Imler JL,Gay NJ

更新日期：2003-08-01 00:00:00

abstract：:Programmed cell death is essential for the development and maintenance of cellular homeostasis of the immune system. The Bcl-2 family of proteins comprises both pro-apoptotic and anti-apoptotic members. A subset of pro-apoptotic members, called 'BH3-only' proteins, share sequence homology only in the minimal death dom...

journal_title：Nature immunology

authors： Opferman JT,Korsmeyer SJ

更新日期：2003-05-01 00:00:00

abstract：:The Drosophila immune system discriminates between different classes of infectious microbes and responds with pathogen-specific defense reactions through selective activation of the Toll and the immune deficiency (Imd) signaling pathways. The Toll pathway mediates most defenses against Gram-positive bacteria and fungi...

journal_title：Nature immunology

authors： Leulier F,Parquet C,Pili-Floury S,Ryu JH,Caroff M,Lee WJ,Mengin-Lecreulx D,Lemaitre B

更新日期：2003-05-01 00:00:00

abstract：:Toll-like receptor-4 activation by lipopolysaccharide (LPS) induces the expression of interferon-beta (IFN-beta) in a MyD88-independent manner. Here we report that mice devoid of the JAK protein tyrosine kinase family member, Tyk2, were resistant to shock induced by high doses of LPS. Basal and LPS-induced expression ...

journal_title：Nature immunology

authors： Karaghiosoff M,Steinborn R,Kovarik P,Kriegshäuser G,Baccarini M,Donabauer B,Reichart U,Kolbe T,Bogdan C,Leanderson T,Levy D,Decker T,Müller M

更新日期：2003-05-01 00:00:00

abstract：:The transcription factor X-box binding protein 1 (XBP-1) is essential for the differentiation of plasma cells and the unfolded protein response (UPR). Here we show that UPR-induced splicing of XBP-1 by the transmembrane endonuclease IRE1 is required to restore production of immunoglobulin in XBP-1-/- mouse B cells, pr...

journal_title：Nature immunology

authors： Iwakoshi NN,Lee AH,Vallabhajosyula P,Otipoby KL,Rajewsky K,Glimcher LH

更新日期：2003-04-01 00:00:00

abstract：:Two potential outcomes confront proliferating antigen-stimulated naive T cells: differentiation to effector and memory cells, or deletion. How stimulation affects cell fate is unclear. Autonomous CD8+ T cell differentiation has been proposed, but this does not explain the abortive proliferation of T cells induced by i...

journal_title：Nature immunology

authors： Gett AV,Sallusto F,Lanzavecchia A,Geginat J

更新日期：2003-04-01 00:00:00

abstract：:Phosphoinositide 3-kinase (PI3K) and phosphatase and tensin homolog (PTEN) phosphatase serve essential functions in the regulation of cell growth, differentiation and survival by modulating intracellular phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P3) concentrations. Here we show that the conditional deletion o...

journal_title：Nature immunology

authors： Anzelon AN,Wu H,Rickert RC

更新日期：2003-03-01 00:00:00

abstract：:We report here the identification of a ligand-receptor system that, upon engagement, leads to the establishment of an antiviral state. Three closely positioned genes on human chromosome 19 encode distinct but paralogous proteins, which we designate interferon-lambda1 (IFN-lambda1), IFN-lambda2 and IFN-lambda3 (tentati...

journal_title：Nature immunology

authors： Kotenko SV,Gallagher G,Baurin VV,Lewis-Antes A,Shen M,Shah NK,Langer JA,Sheikh F,Dickensheets H,Donnelly RP

更新日期：2003-01-01 00:00:00

abstract：:CD4+ T cell priming under T helper type I (T(H)1) or T(H)2 conditions gives rise to polarized cytokine gene expression. We found that in these conditions human naive T cells acquired stable histone hyperacetylation at either the Ifng or Il4 promoter. Effector memory T cells showed polarized cytokine gene acetylation p...

journal_title：Nature immunology

authors： Messi M,Giacchetto I,Nagata K,Lanzavecchia A,Natoli G,Sallusto F

更新日期：2003-01-01 00:00:00

abstract：:Oxidants such as H2O2 are connected to lymphocyte activation, but the molecular mechanisms behind this phenomenon are less clear. Here, I review data suggesting that by inhibiting protein tyrosine phosphatases, H2O2 plays an important role as a secondary messenger in the initiation and amplification of signaling at th...

journal_title：Nature immunology

authors： Reth M

更新日期：2002-12-01 00:00:00

abstract：:Endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) appears to be specialized to produce peptides presented on class I major histocompatibility complex molecules. We found that purified ERAP1 trimmed peptides that were ten residues or longer, but spared eight-residue peptides. In vivo, ERAP1 enhanced production of an ...

journal_title：Nature immunology

authors： York IA,Chang SC,Saric T,Keys JA,Favreau JM,Goldberg AL,Rock KL

更新日期：2002-12-01 00:00:00

abstract：:It is unclear why immunological control of HIV replication is incomplete in most infected individuals. We examined here the CD8+ T cell response to HIV-infected CD4+ T cells in rare patients with immunological control of HIV. Although high frequencies of HIV-specific CD8+ T cells were present in nonprogressors and pro...

journal_title：Nature immunology

authors： Migueles SA,Laborico AC,Shupert WL,Sabbaghian MS,Rabin R,Hallahan CW,Van Baarle D,Kostense S,Miedema F,McLaughlin M,Ehler L,Metcalf J,Liu S,Connors M

更新日期：2002-11-01 00:00:00

abstract：:CD8+ T cells play an important role in immunity to viruses. Just how important these cells are is demonstrated by the evolution of viral strategies for blocking the generation or display of peptide-major histocompatibility complex class I complexes on the surfaces of virus-infected cells. Here, we focus on viral inter...

journal_title：Nature immunology

authors： Yewdell JW,Hill AB

更新日期：2002-11-01 00:00:00

abstract：:The ability of HIV-1 to use dendritic cells (DCs) for transport and to transfer virus to activated T cells in the lymph node may be crucial in early HIV-1 pathogenesis. We have characterized primary DCs for the receptors involved in viral envelope attachment and observed that C-type lectin receptor (CLR) binding was p...

journal_title：Nature immunology

authors： Turville SG,Cameron PU,Handley A,Lin G,Pöhlmann S,Doms RW,Cunningham AL

更新日期：2002-10-01 00:00:00

abstract：:During the productive interaction of T cells with antigen-presenting cells (APCs), engaged receptors, including the T cell antigen receptors and their associated tyrosine kinases, assemble into spatially segregated supramolecular activation clusters (SMACs) at the area of cell contact. Here, we studied intracellular s...

journal_title：Nature immunology

authors： Freiberg BA,Kupfer H,Maslanik W,Delli J,Kappler J,Zaller DM,Kupfer A

更新日期：2002-10-01 00:00:00

abstract：:The signaling pathways that regulate B and T lymphocytes are remarkably conserved between humans and mice. However, recent evidence suggests that the pathways regulating natural killer (NK) cell activation may actually differ between these two species. We discuss the controversies in the field and propose that this di...

journal_title：Nature immunology

authors： Colucci F,Di Santo JP,Leibson PJ

更新日期：2002-09-01 00:00:00

abstract：:CARMA1 is a lymphocyte-specific member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins, which coordinate signaling pathways emanating from the plasma membrane. CARMA1 interacts with Bcl10 via its caspase-recruitment domain (CARD). Here we investigated the role of CARMA1 in T cell act...

journal_title：Nature immunology

authors： Gaide O,Favier B,Legler DF,Bonnet D,Brissoni B,Valitutti S,Bron C,Tschopp J,Thome M

更新日期：2002-09-01 00:00:00

abstract：:Fc epsilon RI activation of mast cells is thought to involve Lyn and Syk kinases proximal to the receptor and the signaling complex organized by the linker for activation of T cells (LAT). We report here that Fc epsilon RI also uses a Fyn kinase-dependent pathway that does not require Lyn kinase or the adapter LAT for...

journal_title：Nature immunology

authors： Parravicini V,Gadina M,Kovarova M,Odom S,Gonzalez-Espinosa C,Furumoto Y,Saitoh S,Samelson LE,O'Shea JJ,Rivera J

更新日期：2002-08-01 00:00:00

abstract：:CD46 is a widely expressed transmembrane protein that was initially identified as binding and inactivating C3b and C4b complement products. We used mice that were transgenic for one of two human CD46 isoforms that differ in their cytoplasmic domains (termed CD46-1 and CD46-2) to analyze the effect of CD46 stimulation ...

journal_title：Nature immunology

authors： Marie JC,Astier AL,Rivailler P,Rabourdin-Combe C,Wild TF,Horvat B

更新日期：2002-07-01 00:00:00

abstract：:Mice deficient for paired immunoglobulin (Ig)-like receptor B (PIR-B) show defective regulation of receptor-mediated activation in antigen-presenting cells. Older PIR-B(-/-) mice had an increased number of peritoneal B1 cells. Splenic PIR-B(-/-) B2 cells were constitutively activated and proliferated much more than th...

journal_title：Nature immunology

authors： Ujike A,Takeda K,Nakamura A,Ebihara S,Akiyama K,Takai T

更新日期：2002-06-01 00:00:00

abstract：:A transgenic reporter mouse strain, which expressed the human CD25 (hCD25) surface marker as a reporter under the control of the pre-T cell receptor alpha(pTalpha) promoter, was used to identify lymphoid precursors that expressed pTalpha intracellularly. The hCD25 reporter marked intra- and extrathymic precursors of l...

journal_title：Nature immunology

authors： Gounari F,Aifantis I,Martin C,Fehling HJ,Hoeflinger S,Leder P,von Boehmer H,Reizis B

更新日期：2002-05-01 00:00:00

abstract：:Recent studies have highlighted the structural requirements for T cell costimulation and have revealed unusual modes of dimerization for the cytolytic T lymphocyte-associated antigen 4 (CTLA-4) costimulatory receptor and its B7 ligands. These distinctive quaternary structures potentially endow both receptor and ligand...

journal_title：Nature immunology

authors： Schwartz JC,Zhang X,Nathenson SG,Almo SC

更新日期：2002-05-01 00:00:00

abstract：:CD1 proteins present various glycolipid antigens to T cells, but the cellular mechanisms that control which particular glycolipids generate T cell responses are not understood. We show here that T cell recognition of glucose monomycolate antigens with long (C(80)) alkyl chains involves the delivery of CD1b proteins an...

journal_title：Nature immunology

authors： Moody DB,Briken V,Cheng TY,Roura-Mir C,Guy MR,Geho DH,Tykocinski ML,Besra GS,Porcelli SA

更新日期：2002-05-01 00:00:00

abstract：:The kappa intronic (MiE(kappa)) and 3' (3'E(kappa)) enhancers are both quantitatively important to, but not essential for, immunoglobulin kappa rearrangement. To determine the functional redundancy between these two enhancers, B cells derived from mutant embryonic stem cells--in which both MiE(kappa) and 3'E(kappa) we...

journal_title：Nature immunology

authors： Inlay M,Alt FW,Baltimore D,Xu Y

更新日期：2002-05-01 00:00:00

abstract：:CD25(+)CD4(+) regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance. We show here that glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR, also known as TNFRSF18)--a member of the tumor necrosis factor-nerve growth factor (TNF-NGF) receptor gen...

journal_title：Nature immunology

authors： Shimizu J,Yamazaki S,Takahashi T,Ishida Y,Sakaguchi S

更新日期：2002-02-01 00:00:00

abstract：:T cells compete in the response to antigen in vivo and this competition may drive the affinity maturation of a secondary T cell response. Here we show that high-affinity T cells out-competed lower affinity T cells during a response to antigenic challenge in vivo. Although competition between T cells specific for diffe...

journal_title：Nature immunology

authors： Kedl RM,Schaefer BC,Kappler JW,Marrack P

更新日期：2002-01-01 00:00:00

abstract：:Plasma cells are cellular factories devoted entirely to the manufacture and export of a single product: soluble immunoglobulin (Ig). As the final mediators of a humoral response, plasma cells play a critical role in adaptive immunity. Although intense effort has been devoted to studying the regulation and requirements...

journal_title：Nature immunology

authors： Calame KL

更新日期：2001-12-01 00:00:00

abstract：:Cytomegalovirus (CMV), measles and HIV are the main human pathogens known to induce immunosuppression. Unlike measles and HIV, and despite the availability of a well studied animal model, little is known about the mechanisms that control CMV-induced immunosuppression. We hypothesized that dendritic cells (DCs), which ...

journal_title：Nature immunology

authors： Andrews DM,Andoniou CE,Granucci F,Ricciardi-Castagnoli P,Degli-Esposti MA

更新日期：2001-11-01 00:00:00

abstract：:We identified a tumor-associated cytotoxic T lymphocyte (CTL) epitope derived from the widely expressed human MDM2 oncoprotein and were able to bypass self-tolerance to this tumor antigen in HLA-A*0201 (A2.1) transgenic mice and by generating A2.1-negative, allo-A2.1-restricted human T lymphocytes. A broad range of ma...

journal_title：Nature immunology

authors： Stanislawski T,Voss RH,Lotz C,Sadovnikova E,Willemsen RA,Kuball J,Ruppert T,Bolhuis RL,Melief CJ,Huber C,Stauss HJ,Theobald M

更新日期：2001-10-01 00:00:00

abstract：:Susceptibility to complex autoimmune diseases (AIDs) is a multigenic phenotype affected by a variety of genetic and environmental or stochastic factors. After over a decade of linkage analyses, the identification of non-major histocompatibility complex (non-MHC) susceptibility alleles has proved to be difficult, predo...

journal_title：Nature immunology

authors： Wandstrat A,Wakeland E

更新日期：2001-09-01 00:00:00

abstract：:Mechanisms that underlie the patterning of cytokine expression in T helper (T(H)) cell subsets remain incompletely defined. An evolutionarily conserved approximately 400-bp noncoding sequence in the intergenic region between the genes Il4 and Il13, designated conserved noncoding sequence 1 (CNS-1), was deleted in mice...

journal_title：Nature immunology

authors： Mohrs M,Blankespoor CM,Wang ZE,Loots GG,Afzal V,Hadeiba H,Shinkai K,Rubin EM,Locksley RM

更新日期：2001-09-01 00:00:00

abstract：:Chemokines are chemoattractant proteins that are divided into subfamilies based upon cysteine signature motifs termed C, CC, CXC and CX3C. Chemokines have roles in immunity and inflammation that affect cell trafficking and activation of T cells as well as cells of the innate immune system. We report here CX3C chemokin...

journal_title：Nature immunology

authors： Tripp RA,Jones LP,Haynes LM,Zheng H,Murphy PM,Anderson LJ

更新日期：2001-08-01 00:00:00

abstract：:We define here the specificity and significance of proteases in the endoplasmic reticulum (ER) that generate peptides for presentation by major histocompatibility complex (MHC) class I molecules. We show that aminopeptidases efficiently trimmed all residues except proline that flank the NH2-termini of antigenic precur...

journal_title：Nature immunology

authors： Serwold T,Gaw S,Shastri N

更新日期：2001-07-01 00:00:00