Asymmetric redundancy in CD4 silencer function.


:We and others have defined a transcriptional silencer critical for the proper expression of the CD4 gene at all stages of T cell development. In this report, we use biochemical techniques to identify three different factor-binding sites within the CD4 silencer, denoted sites I, II, and III. Using transgenic analyses, we determine that although all three factor-binding sites are important for silencer activity, there is significant redundancy in that the presence of either site II alone, or the combination of sites I and III permits silencer function. Thus, our data indicate that the mechanism of function of the CD4 silencer is extremely complex. Further biochemical analyses indicate that the factor binding to site II has the same sequence specificity as a factor binding to an E box site in the CD4 enhancer; thus, a member of the bHLH factor family may be important in mediating silencer function.






Duncan DD,Adlam M,Siu G




Has Abstract


1996-03-01 00:00:00
















  • Elimination of germinal-center-derived self-reactive B cells is governed by the location and concentration of self-antigen.

    abstract::Secondary diversification of the B cell repertoire by immunoglobulin gene somatic hypermutation in the germinal center (GC) is essential for providing the high-affinity antibody specificities required for long-term humoral immunity. While the risk to self-tolerance posed by inadvertent generation of self-reactive GC B...


    pub_type: 杂志文章


    authors: Chan TD,Wood K,Hermes JR,Butt D,Jolly CJ,Basten A,Brink R

    更新日期:2012-11-16 00:00:00

  • Direct presentation of nonpeptide prenyl pyrophosphate antigens to human gamma delta T cells.

    abstract::Human V gamma 2V delta 2+ T cells recognize mycobacterial nonpeptide antigens, such as isopentenyl pyrophosphate, and their synthetic analogs, such as monoethyl phosphate, through a TCR-dependent process. Here, we examine the presentation of these antigens. V gamma 2V delta 2+ T cells recognized secreted prenyl pyroph...


    pub_type: 杂志文章


    authors: Morita CT,Beckman EM,Bukowski JF,Tanaka Y,Band H,Bloom BR,Golan DE,Brenner MB

    更新日期:1995-10-01 00:00:00

  • Inflammasome-mediated disease animal models reveal roles for innate but not adaptive immunity.

    abstract::NLRP3 nucleates the inflammasome, a protein complex responsible for cleavage of prointerleukin-1beta (IL-1beta) to its active form. Mutations in the NLRP3 gene cause the autoinflammatory disease spectrum cryopyrin-associated periodic syndromes (CAPS). The central role of IL-1beta in CAPS is supported by the response t...


    pub_type: 杂志文章


    authors: Brydges SD,Mueller JL,McGeough MD,Pena CA,Misaghi A,Gandhi C,Putnam CD,Boyle DL,Firestein GS,Horner AA,Soroosh P,Watford WT,O'Shea JJ,Kastner DL,Hoffman HM

    更新日期:2009-06-19 00:00:00

  • Control of T helper 2 responses by transcription factor IRF4-dependent dendritic cells.

    abstract::CD4⁺ T cell differentiation is regulated by specialized antigen-presenting cells. Dendritic cells (DCs) produce cytokines that promote naive CD4⁺ T cell differentiation into T helper 1 (Th1), Th17, and inducible T regulatory (iTreg) cells. However, the initiation of Th2 cell responses remains poorly understood, althou...


    pub_type: 杂志文章


    authors: Gao Y,Nish SA,Jiang R,Hou L,Licona-Limón P,Weinstein JS,Zhao H,Medzhitov R

    更新日期:2013-10-17 00:00:00

  • A single subset of dendritic cells controls the cytokine bias of natural killer T cell responses to diverse glycolipid antigens.

    abstract::Many hematopoietic cell types express CD1d and are capable of presenting glycolipid antigens to invariant natural killer T cells (iNKT cells). However, the question of which cells are the principal presenters of glycolipid antigens in vivo remains controversial, and it has been suggested that this might vary depending...


    pub_type: 杂志文章


    authors: Arora P,Baena A,Yu KO,Saini NK,Kharkwal SS,Goldberg MF,Kunnath-Velayudhan S,Carreño LJ,Venkataswamy MM,Kim J,Lazar-Molnar E,Lauvau G,Chang YT,Liu Z,Bittman R,Al-Shamkhani A,Cox LR,Jervis PJ,Veerapen N,Besra GS,Por

    更新日期:2014-01-16 00:00:00

  • Dendritic cells permit identification of genes encoding MHC class II-restricted epitopes of transplantation antigens.

    abstract::Minor or histocompatibility (H) antigens are recognized by CD4+ and CD8+ T lymphocytes as short polymorphic peptides associated with MHC molecules. They are the targets of graft versus host and graft versus leukemia responses following bone marrow transplantation between HLA-identical siblings. Several genes encoding ...


    pub_type: 杂志文章


    authors: Scott D,Addey C,Ellis P,James E,Mitchell MJ,Saut N,Jurcevic S,Simpson E

    更新日期:2000-06-01 00:00:00

  • NLRC3 puts the brakes on STING.

    abstract::NOD-like receptors (NLRs) are increasingly implicated in regulating pathogen-sensing pathways. In this issue of Immunity, Zhang et al. (2014) describe a role for NLRC3 in regulating STING and the inflammatory response to cytosolic DNA. ...


    pub_type: 评论,杂志文章


    authors: Mangan MS,Latz E

    更新日期:2014-03-20 00:00:00

  • Key role of flt3 ligand in regulation of the common lymphoid progenitor but not in maintenance of the hematopoietic stem cell pool.

    abstract::The first lineage commitment step of hematopoietic stem cells (HSC) results in separation into distinct lymphoid and myeloid differentiation pathways, reflected in the generation of common lymphoid and myeloid progenitors (CLP and CMP, respectively). In this report we present the first evidence for a nonredundant regu...


    pub_type: 杂志文章


    authors: Sitnicka E,Bryder D,Theilgaard-Mönch K,Buza-Vidas N,Adolfsson J,Jacobsen SE

    更新日期:2002-10-01 00:00:00

  • Functional assessment of precursors from murine bone marrow suggests a sequence of early B lineage differentiation events.

    abstract::Most lineage marker-negative (Lin-)TdT+ cells from murine marrow lack CD34 but display c-kit at low density as well as IL-7Ralpha and Flk-2/Flt-3 receptors. Single cells with these characteristics generated CD45RA+CD19- as well as CD19+ lymphocytes in culture. CD45RA+CD19- marrow cells were resolved into three nonover...


    pub_type: 杂志文章


    authors: Tudor KS,Payne KJ,Yamashita Y,Kincade PW

    更新日期:2000-03-01 00:00:00

  • Neonatal injection of an ovarian peptide induces autoimmune ovarian disease in female mice: requirement of endogenous neonatal ovaries.

    abstract::Neonatal female mice injected with the self ZP3 peptide are not tolerant to the peptide; they develop autoimmune ovarian disease (AOD) and autoantibody response 5 weeks later. ZP3 challenge leads to severe AOD and ZP3-specific T cell and antibody responses. In contrast, neonatal tolerance to foreign ZP3 peptide is est...


    pub_type: 杂志文章


    authors: Garza KM,Griggs ND,Tung KS

    更新日期:1997-01-01 00:00:00

  • Antisocial networking in T helper cells.

    abstract::T helper cell differentiation is controlled by a network of transcription factors. In this issue of Immunity, Yagi et al. (2010) describe the opposing effects of transcription factors Runx3 and GATA3 in the network promoting T helper 1 cell development. ...


    pub_type: 评论,杂志文章


    authors: Pham D,Kaplan MH

    更新日期:2010-04-23 00:00:00

  • Illuminating the black box of TNF action in tuberculous granulomas.

    abstract::TNF clearly contributes to immunity to intracellular pathogens, but how it does so is incompletely understood. In this issue of Immunity, Clay et al. (2008) provide unique insights, using intravital microscopy and the zebrafish-embryo model of tuberculosis. ...


    pub_type: 评论,杂志文章


    authors: Miller EA,Ernst JD

    更新日期:2008-08-15 00:00:00

  • Regulatory T cells sequentially migrate from inflamed tissues to draining lymph nodes to suppress the alloimmune response.

    abstract::To determine the site and mechanism of suppression by regulatory T (Treg) cells, we investigated their migration and function in an islet allograft model. Treg cells first migrated from blood to the inflamed allograft where they were essential for the suppression of alloimmunity. This process was dependent on the chem...


    pub_type: 杂志文章


    authors: Zhang N,Schröppel B,Lal G,Jakubzick C,Mao X,Chen D,Yin N,Jessberger R,Ochando JC,Ding Y,Bromberg JS

    更新日期:2009-03-20 00:00:00

  • Cyclic GMP-AMP synthase is activated by double-stranded DNA-induced oligomerization.

    abstract::Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor mediating innate antimicrobial immunity. It catalyzes the synthesis of a noncanonical cyclic dinucleotide, 2',5' cGAMP, that binds to STING and mediates the activation of TBK1 and IRF-3. Activated IRF-3 translocates to the nucleus and initiates the transcription...


    pub_type: 杂志文章


    authors: Li X,Shu C,Yi G,Chaton CT,Shelton CL,Diao J,Zuo X,Kao CC,Herr AB,Li P

    更新日期:2013-12-12 00:00:00

  • DEER Spectroscopy Measurements Reveal Multiple Conformations of HIV-1 SOSIP Envelopes that Show Similarities with Envelopes on Native Virions.

    abstract::HIV-1 Envelope (Env) mediates viral-host membrane fusion after binding host-receptor CD4 and coreceptor. Soluble envelopes (SOSIPs), designed to mimic prefusion conformational states of virion-bound envelopes, are proposed immunogens for eliciting neutralizing antibodies, yet only static structures are available. To e...


    pub_type: 杂志文章


    authors: Stadtmueller BM,Bridges MD,Dam KM,Lerch MT,Huey-Tubman KE,Hubbell WL,Bjorkman PJ

    更新日期:2018-08-21 00:00:00

  • Central tolerance matters.

    abstract::In this issue of Immunity, Anderson et al. provide another clue to the riddle that is Aire--why do human beings and mice lacking Aire develop diffuse and pathogenic autoimmunity? They find that Aire influences central tolerance not only by promoting the expression of peripheral self-proteins in thymic medullary epithe...


    pub_type: 评论,杂志文章,评审


    authors: Goldrath AW,Hedrick SM

    更新日期:2005-08-01 00:00:00

  • Oral infection drives a distinct population of intestinal resident memory CD8(+) T cells with enhanced protective function.

    abstract::The intestinal mucosa promotes T cell responses that might be beneficial for effective mucosal vaccines. However, intestinal resident memory T (Trm) cell formation and function are poorly understood. We found that oral infection with Listeria monocytogenes induced a robust intestinal CD8 T cell response and blocking e...


    pub_type: 杂志文章


    authors: Sheridan BS,Pham QM,Lee YT,Cauley LS,Puddington L,Lefrançois L

    更新日期:2014-05-15 00:00:00

  • Spatial separation of HLA-DM/HLA-DR interactions within MIIC and phagosome-induced immune escape.

    abstract::Major Histocompatibility Complex (MHC) class II molecules, including Human Leukocyte Antigen (HLA)-DR, present peptide fragments from proteins degraded in the endocytic pathway. HLA-DR is targeted to late-endocytic structures named MHC class II-containing Compartments (MIIC), where it interacts with HLA-DM. This chape...


    pub_type: 杂志文章


    authors: Zwart W,Griekspoor A,Kuijl C,Marsman M,van Rheenen J,Janssen H,Calafat J,van Ham M,Janssen L,van Lith M,Jalink K,Neefjes J

    更新日期:2005-02-01 00:00:00

  • Viral infection results in massive CD8+ T cell expansion and mortality in vaccinated perforin-deficient mice.

    abstract::Perforin-mediated cytotoxicity is essential for clearance of primary LCMV infection. BALB/c-perforin-deficient (PKO) mice survived LCMV infection by deleting NP(118)-specific CD8(+) T cells whereas vaccination of PKO mice with Listeria expressing NP(118) generated a stable memory CD8(+) T cell population. However, >85...


    pub_type: 杂志文章


    authors: Badovinac VP,Hamilton SE,Harty JT

    更新日期:2003-04-01 00:00:00

  • The continuum of cancer immunosurveillance: prognostic, predictive, and mechanistic signatures.

    abstract::Numerous analyses of large patient cohorts identified specific patterns of immune activation associated with patient survival. We established these as the immune contexture, encompassing the type, functional orientation, density, and location of adaptive immune cells within distinct tumor regions. Based on the immune ...


    pub_type: 杂志文章,评审


    authors: Galon J,Angell HK,Bedognetti D,Marincola FM

    更新日期:2013-07-25 00:00:00

  • Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia.

    abstract::Colony stimulating factor-1 (Csf-1) receptor and its ligand Csf-1 control macrophage development, maintenance, and function. The development of both Langerhans cells (LCs) and microglia is highly dependent on Csf-1 receptor signaling but independent of Csf-1. Here we show that in both mice and humans, interleukin-34 (...


    pub_type: 杂志文章


    authors: Greter M,Lelios I,Pelczar P,Hoeffel G,Price J,Leboeuf M,Kündig TM,Frei K,Ginhoux F,Merad M,Becher B

    更新日期:2012-12-14 00:00:00

  • IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells.

    abstract::An efficient Th1-driven adaptive immune response requires activation of the T cell receptor and secretion of the T cell stimulatory cytokine IL-12 by activated antigen-presenting cells. IL-12 triggers Th1 polarization of naive CD4(+) T cells and secretion of IFN-gamma. We describe a new heterodimeric cytokine termed I...


    pub_type: 杂志文章


    authors: Pflanz S,Timans JC,Cheung J,Rosales R,Kanzler H,Gilbert J,Hibbert L,Churakova T,Travis M,Vaisberg E,Blumenschein WM,Mattson JD,Wagner JL,To W,Zurawski S,McClanahan TK,Gorman DM,Bazan JF,de Waal Malefyt R,Rennick D,

    更新日期:2002-06-01 00:00:00

  • A Little Fiber Goes a Long Way.

    abstract::In this issue of Immunity, Trompette et al. (2018) show that dietary fiber and short chain fatty acids reduce influenza A virus-associated immunopathology by enhancing CD8+ T cell effector function and by promoting the differentiation of alternatively activated macrophages. ...


    pub_type: 评论,杂志文章


    authors: Castillo PAC,Hand TW

    更新日期:2018-05-15 00:00:00

  • IgM Memory Cells: First Responders in Malaria.

    abstract::Following the fate of antigen-specific memory B cells has been difficult. In this issue of Immunity, Krishnamurty et al. (2016) use a novel B cell tetramer to define Plasmodium-specific memory B cells in parasite-infected mice and demonstrate that after re-infection, somatically mutated IgM(+) memory B cells function ...


    pub_type: 评论,杂志文章


    authors: Stone SL,Lund FE

    更新日期:2016-08-16 00:00:00

  • Memory T cell RNA rearrangement programmed by heterogeneous nuclear ribonucleoprotein hnRNPLL.

    abstract::Differentiation of memory cells involves DNA-sequence changes in B lymphocytes but is less clearly defined in T cells. RNA rearrangement is identified here as a key event in memory T cell differentiation by analysis of a mouse mutation that altered the proportions of naive and memory T cells and crippled the process o...


    pub_type: 杂志文章


    authors: Wu Z,Jia X,de la Cruz L,Su XC,Marzolf B,Troisch P,Zak D,Hamilton A,Whittle B,Yu D,Sheahan D,Bertram E,Aderem A,Otting G,Goodnow CC,Hoyne GF

    更新日期:2008-12-19 00:00:00

  • ICOS coreceptor signaling inactivates the transcription factor FOXO1 to promote Tfh cell differentiation.

    abstract::T follicular helper (Tfh) cells are essential in the induction of high-affinity, class-switched antibodies. The differentiation of Tfh cells is a multi-step process that depends upon the co-receptor ICOS and the activation of phosphoinositide-3 kinase leading to the expression of key Tfh cell genes. We report that ICO...


    pub_type: 杂志文章


    authors: Stone EL,Pepper M,Katayama CD,Kerdiles YM,Lai CY,Emslie E,Lin YC,Yang E,Goldrath AW,Li MO,Cantrell DA,Hedrick SM

    更新日期:2015-02-17 00:00:00

  • Dysregulated Expression of the Nuclear Exosome Targeting Complex Component Rbm7 in Nonhematopoietic Cells Licenses the Development of Fibrosis.

    abstract::Fibrosis is an incurable disorder of unknown etiology. Segregated-nucleus-containing atypical monocytes (SatMs) are critical for the development of fibrosis. Here we examined the mechanisms that recruit SatMs to pre-fibrotic areas. A screen based on cytokine expression in the fibrotic lung revealed that the chemokine ...


    pub_type: 杂志文章


    authors: Fukushima K,Satoh T,Sugihara F,Sato Y,Okamoto T,Mitsui Y,Yoshio S,Li S,Nojima S,Motooka D,Nakamura S,Kida H,Standley DM,Morii E,Kanto T,Yanagita M,Matsuura Y,Nagasawa T,Kumanogoh A,Akira S

    更新日期:2020-03-17 00:00:00

  • Differential expression of interleukin-17A and -17F is coupled to T cell receptor signaling via inducible T cell kinase.

    abstract::T helper 17 (Th17) cells play major roles in autoimmunity and bacterial infections, yet how T cell receptor (TCR) signaling affects Th17 cell differentiation is relatively unknown. We demonstrate that CD4(+) T cells lacking Itk, a tyrosine kinase required for full TCR-induced phospholipase C-gamma (PLC-gamma1) activat...


    pub_type: 杂志文章


    authors: Gomez-Rodriguez J,Sahu N,Handon R,Davidson TS,Anderson SM,Kirby MR,August A,Schwartzberg PL

    更新日期:2009-10-16 00:00:00

  • Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells.

    abstract::The interferon-producing plasmacytoid dendritic cells (pDCs) share common progenitors with antigen-presenting classical dendritic cells (cDCs), yet they possess distinct morphology and molecular features resembling those of lymphocytes. It is unclear whether the unique cell fate of pDCs is actively maintained in the s...


    pub_type: 杂志文章


    authors: Ghosh HS,Cisse B,Bunin A,Lewis KL,Reizis B

    更新日期:2010-12-14 00:00:00

  • Apoptosis regulators Fas and Bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity.

    abstract::Apoptotic death of T lymphocytes is critical for shutdown of immune responses and hemopoietic cell homeostasis. Both death receptor (Fas) activation and mitochondrial apoptosis triggered by the BH3-only protein Bim have been implicated in the killing of antigen-stimulated T cells. We examined mice lacking the gene enc...


    pub_type: 杂志文章


    authors: Hughes PD,Belz GT,Fortner KA,Budd RC,Strasser A,Bouillet P

    更新日期:2008-02-01 00:00:00