Abstract:
:The pool of hematopoietic stem cells (HSCs) in the bone marrow is a mixture of resting, proliferating, and differentiating cells. Long-term repopulating HSCs (LT-HSC) are routinely enriched as Lin- Sca1+ c-Kit+ CD34- Flt3- CD150+ CD48- cells. The Flt3 ligand (Flt3L) and its receptor Flt3 are important regulators of HSC maintenance, expansion and differentiation. Using Flt3L-eGFP reporter mice, we show that endogenous Flt3L-eGFP-reporter RNA expression correlates with eGFP-protein expression. This Flt3L-eGFP-reporter expression distinguishes two LT-HSC populations with differences in gene expressions and reconstituting potential. Thus, Flt3L-eGFP-reporterlow cells are identified as predominantly resting HSCs with long-term repopulating capacities. In contrast, Flt3L-eGFP-reporterhigh cells are in majority proliferating HSCs with only short-term repopulating capacities. Flt3L-eGFP-reporterlow cells express hypoxia, autophagy-inducing, and the LT-HSC-associated genes HoxB5 and Fgd5, while Flt3L-eGFP-reporterhigh HSCs upregulate genes involved in HSC differentiation. Flt3L-eGFP-reporterlow cells develop to Flt3L-eGFP-reporterhigh cells in vitro, although Flt3L-eGFP-reporterhigh cells remain Flt3L-eGFP-reporterhigh . CD150+ Flt3L-eGFP-reporterlow cells express either endothelial protein C receptor (EPCR) or CD41, while Flt3L-eGFP-reporterhigh cells do express EPCR but not CD41. Thus, FACS-enrichment of Flt3/ Flt3L-eGFP-reporter negative, Lin- CD150+ CD48- EPCR+ CD41+ HSCs allows a further 5-fold enrichment of functional LT-HSCs.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Tornack J,Kawano Y,Garbi N,Hämmerling GJ,Melchers F,Tsuneto Mdoi
10.1002/eji.201646730subject
Has Abstractpub_date
2017-09-01 00:00:00pages
1477-1487issue
9eissn
0014-2980issn
1521-4141journal_volume
47pub_type
杂志文章abstract::Chronic skin inflammation resulting from a defective epidermal barrier is a hallmark of atopic dermatitis (AD). We previously demonstrated that mice lacking FGF receptors 1 and 2 in keratinocytes (K5-R1/R2 mice) develop an AD-like chronic dermatitis as a result of an impaired epidermal barrier. Here, we show that γδ T...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201545675
更新日期:2015-09-01 00:00:00
abstract::Interleukin-12 family cytokines have emerged as critical regulators of immunity with some members (IL-12, IL-23) associated with disease pathogenesis while others (IL-27, IL-35) mitigate autoimmune diseases. Each IL-12 family member is comprised of an α and a β chain, and chain-sharing is a key feature. Although four ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201546095
更新日期:2016-06-01 00:00:00
abstract::Spontaneous apoptosis in germinal center (GC) B cells can be arrested either by engaging cell surface immunoglobulin (Ig) with immobilized ligand or, more effectively, by treatment with soluble monoclonal antibody (mAb) directed against CD40. The present study examines the intracellular signal transduction pathways th...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830231030
更新日期:1993-10-01 00:00:00
abstract::The stimulatory as well as the inhibitory capacity of alloantisera has been investigated with respect to rat mast cell functions. Alloantibody against alloantigens coded for by the major histocompatibility (H-1) gene region promoted histamine release from purified LEW mast cells. This process was found to be complemen...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830060813
更新日期:1976-08-01 00:00:00
abstract::The TORC1 pathway is necessary for ribosomal biogenesis and initiation of protein translation. Furthermore, the differentiation of Th1 and Th17 cells requires TORC1 activity. To investigate the role of the TORC1 pathway in the differentiation of Th1 and/or Th17 cells in more detail, we compared the differentiation cap...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201445422
更新日期:2016-01-01 00:00:00
abstract::In this study we examined the effect of interleukin 4 (IL 4) on T cell activation and proliferation via the alternative CD2 pathway. To this end highly purified human resting T cells were cultured with a stimulating pair of anti-CD2 monoclonal antibodies in the absence of accessory signals from monocytes. Addition of ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830200724
更新日期:1990-07-01 00:00:00
abstract::Interleukin 2 (IL2)-dependent cytolytic hybrids usually loose IL2 dependence and cytolytic activity concomittantly. Here we describe an exceptional IL2-independent variant which lost IL2 receptor but retained cytolytic activity. When the IL2-independent cytolytic hybrid cells were fused with IL2-dependent cytolytic cl...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830150803
更新日期:1985-08-01 00:00:00
abstract::T-cell death is a fundamental process that is intricately regulated at multiple phases during T-cell differentiation, tolerance induction and the decline of the immune response. Caspase 3 is a crucial molecule regulating both mitochondrial and death receptor apoptotic pathways and therefore we were interested in exami...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201040475
更新日期:2010-12-01 00:00:00
abstract::CD4+ CD25+ Foxp3+ regulatory T cells (Treg) are natural suppressors of autoimmunity but they can also dampen the effective clearance of infectious organisms. These cells have the potential to be exploited to prevent transplant rejection and to treat autoimmune disease. A paper in this issue of the European Journal of ...
journal_title:European journal of immunology
pub_type: 评论,杂志文章,评审
doi:10.1002/eji.200635967
更新日期:2006-04-01 00:00:00
abstract::In previous studies, Saimiri sciureus boliviensis monkeys have been immunized with four recombinant proteins reproducing part of the circumsporozoite (CS) protein of Plasmodium vivax sporozoites (NS1(81) V20, rPvCS-1, rPvCS-2, rPv-CS-3), or with irradiated sporozoites of P. vivax Salvador I strain. To analyze the anti...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830220234
更新日期:1992-02-01 00:00:00
abstract::Chemokines are proinflammatory mediators that regulate leukocyte trafficking at different steps of the leukocyte recruitment cascade. Studies using new imaging approaches and new mouse models are giving new insights into the role of chemokines in neutrophil migration at sites of inflammation. Conventional rolling and ...
journal_title:European journal of immunology
pub_type: 杂志文章,评审
doi:10.1002/eji.201142231
更新日期:2012-02-01 00:00:00
abstract::Naturally activated T lymphocytes present in normal mouse spleen were studied for direct reactivity to interleukin 2 (IL 2) and for binding of anti-IL 2 receptor (IL 2R) antibodies or radiolabeled IL 2. The majority of large-sized splenic T lymphocytes are IL 2R-; thus, at the most one third of large L3T4+ T cells and...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830170702
更新日期:1987-07-01 00:00:00
abstract::Cofilin, an actin-depolymerizing protein, is essential for the functional dynamics of the actin cytoskeleton and for cell viability. In unstimulated human peripheral blood T lymphocytes cofilin is phosphorylated and localized in the cytoplasm. Following co-stimulation through accessory receptors (e.g. CD2 or CD28) - h...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(2000012)30:12<3422::AID-IMMU3422
更新日期:2000-12-01 00:00:00
abstract::T cell clones of C57BL/6 origin which recognize porcine lactate dehydrogenase B (LDH-BP) together with the Ab molecule were characterized in terms of fine specificity for both LDH-B and self-major histocompatibility complex determinants. Using antigen-presenting cells from the Ab-mutant strain B6.C-H-2bm12 (bm12), thr...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830150814
更新日期:1985-08-01 00:00:00
abstract::Gammadelta T cells are expanded in human IgA nephropathy and in a rat model of adriamycin (ADR)-induced nephropathy. Despite different diseases and species, these renal gammadelta T cells use a restricted set of gammadelta T cell receptor (TCR) genes. To explore whether this phenomenon of post injury expansion of gamm...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200324780
更新日期:2004-08-01 00:00:00
abstract::A method for infection of lymphocytes with Moloney(Abelson) murine leukemia virus [M(A)-MuLV] is described. Only lymphoblasts obtained after stimulation of normal spleen cells by the B cell mitogen lipopolysaccharide (LPS) were satisfactory targets for virus-specific, secondary cytotoxic T lymphocytes (CTL), whereas s...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830110316
更新日期:1981-03-01 00:00:00
abstract::A reverse hemolytic plaque assay has been developed which specifically detects secretion of human immune interferon (Hu IFN-gamma) at the single cell level. Unstimulated peripheral blood lymphocytes from healthy adult volunteers spontaneously secreted IFN-gamma. Stimulation of these cells with concanavalin A, phytohem...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830130308
更新日期:1983-03-01 00:00:00
abstract::Traumatic brain injury (TBI) elicits innate inflammatory responses that can lead to secondary brain injury. To better understand the mechanisms involved in TBI-induced inflammation, we examined the nature of macrophages responding to TBI in mice. In this model, brain macrophages were increased >20-fold the day after i...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201243084
更新日期:2013-08-01 00:00:00
abstract::Human T cell clones expressing the T cell receptor (TcR) gamma/delta were isolated from peripheral blood lymphocytes of two unrelated donors. The TcR gamma/delta+ clones derived from one of these donors were all of the Ti gamma A+, delta-TCS1-, BB3+ phenotype indicating the exclusive use of the V gamma 9 and V delta 3...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830191120
更新日期:1989-11-01 00:00:00
abstract::The structure of immunological synapses formed between murine naive T cells and mature dendritic cells has been subjected to a quantitative analysis. Immunofluorescence images of synapses formed in the absence of antigen show a diffuse synaptic accumulation of CD3 and LFA-1. In electron microscopy, these antigen-free ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200425857
更新日期:2005-06-01 00:00:00
abstract::T cell activation and cytokine secretion are important mediators of inflammation in allergic asthma. The costimulatory pathway CD28/CD80/CD86 has been shown to play an important role in T cell activation in allergic asthma, but less is known about the effect of other costimulatory molecules in allergy. The costimulato...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(2002010)32:10<2874::AID-IMMU2874
更新日期:2002-10-01 00:00:00
abstract::FTY720 is a novel immunosuppressant that improves the outcomes after solid organ and bone marrow transplantation (BMT) due to the sequestration of T cells into LN. We tested the hypothesis that the sequestration of donor T cells in LN by FTY720 would enhance their interaction with host APC, thus causing a greater degr...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200636123
更新日期:2007-01-01 00:00:00
abstract::Ikaros is a transcriptional regulator whose function is essential for B cell development. It is expressed in the hematopoietic stem cell (HSC) through the mature B cell stage. Using genetically engineered mice in which the endogenous Ikaros gene is disrupted, it has been shown that a lack of Ikaros leads to a block in...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200637026
更新日期:2007-04-01 00:00:00
abstract::T lymphocytes can be activated and induced to proliferate through stimulation of the CD2 glycoprotein with functional combinations of CD2 antibodies. However, this mechanism of signal transduction via CD2 is still not fully understood. We have investigated which molecules on the T cell surface preferentially associate...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200205)32:5<1509::AID-IMMU1509>3
更新日期:2002-05-01 00:00:00
abstract::Natural killer (NK) cells play an important role in early defense against viral infection. The cytotoxic activity of NK cells is increased by interferon-alpha/beta (IFN-alpha/beta), produced en masse in virally infected cells. However, the mechanism(s) by which IFN-alpha/beta contribute to the NK-cell-mediated antivir...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200111)31:11<3138::aid-immu3138>
更新日期:2001-11-01 00:00:00
abstract::IL-12 is an important immunomodulatory cytokine that induces tyrosine phosphorylation and activation of the signal transducer and activator of transcription (STAT)4. IL-12 induces sustained activation and nuclear translocation of STAT4 and this regulatory process is coupled to both tyrosine and serine phosphorylation ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(200005)30:5<1425::AID-IMMU
更新日期:2000-05-01 00:00:00
abstract::Activated allergen-specific Th2 and Th1 cells release cytokines that transform neutrophils into functional APCs characterized by the expression of HLA-DR and CD58 as well as enhanced survival and antigen uptake, irrespectively of the presence of IL-10, which reduces allergen uptake by neutrophils. ...
journal_title:European journal of immunology
pub_type: 信件
doi:10.1002/eji.201848057
更新日期:2019-09-01 00:00:00
abstract::Human T cell clones (TCC) are antigen-presenting cells (APC) able to present peptides and superantigens (SAg) and to process and present intact proteins. TCC express major histocompatibility complex (MHC) class II antigens and molecules involved in the accessory signal delivery, such as B7.1 and B7.2/B70. Notwithstand...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830260411
更新日期:1996-04-01 00:00:00
abstract::T cell recognition of self antigens is a key event in the pathogenesis of autoimmune diseases. To date, the initial events that trigger autoreactive T cells are unknown. The "molecular mimicry" hypothesis predicts that during an infection T cells that recognize both a microbial antigen and a related self peptide becom...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200002)30:2<448::AID-IMMU448>3.0
更新日期:2000-02-01 00:00:00
abstract::Glomerular crescent formation characterizes severe glomerulonephritis (GN). Evidence suggests that crescent formation results from a delayed-type hypersensitivity-like Th1 response. As IL-12 directs Th1 responses, we tested the hypothesis that IL-12 is important in crescentic GN. Neutralization of IL-12 attenuated cre...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199901)29:01<1::AID-IMMU1>
更新日期:1999-01-01 00:00:00