Abstract:
:Two families of protein tyrosine kinases (PTKs), the Src and Syk/ZAP-70 families, are required for T cell development. Lck is the major Src family member required for thymopoiesis, since there is a severe deficit of CD4+CD8+ thymocytes and mature T cells in its absence. However, some peripheral T cells are evident in these mice, suggesting that additional PTKs may contribute to T cell development. Here we show that the combined disruption of Lck and Fyn (lck(-/-)fyn(-/-)) completely arrests alpha beta T cell development at the CD4-CD8- stage. The development of V gamma 3+ dendritic epidermal T cells is also severely impaired, but natural killer cell development and cytolytic activity is unaffected in lck(-/-)fyn(-/-) mice. These findings reveal the potential for redundant functions mediated by Src family PTKs while emphasizing crucial roles for Lck and Fyn in T cell development.
journal_name
Immunityjournal_title
Immunityauthors
van Oers NS,Lowin-Kropf B,Finlay D,Connolly K,Weiss Adoi
10.1016/s1074-7613(00)80499-9subject
Has Abstractpub_date
1996-11-01 00:00:00pages
429-36issue
5eissn
1074-7613issn
1097-4180pii
S1074-7613(00)80499-9journal_volume
5pub_type
杂志文章相关文献
IMMUNITY文献大全abstract::The transcription factor GATA3 is crucial for the differentiation of naive CD4(+) T cells into T helper 2 (Th2) cells. Here, we show that deletion of Gata3 allowed the appearance of interferon-gamma (IFN-gamma)-producing cells in the absence of interleukin-12 (IL-12) and IFN-gamma. Such IFN-gamma production was transc...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2010.04.004
更新日期:2010-04-23 00:00:00
abstract::The immunological synapse is characterized by the reorganization of membrane proteins at the immunological synapse. Active cytoskeletal mechanisms are involved in recruiting the TCR, accessory molecules, and the integrin LFA-1 to the contact area. Other molecules like CD43 are excluded from the contact area, but the m...
journal_title:Immunity
pub_type: 杂志文章,评审
doi:10.1016/s1074-7613(01)00237-0
更新日期:2001-11-01 00:00:00
abstract::Infiltration of regulatory T (Treg) cells into many tumor types correlates with poor patient prognoses. However, mechanisms of intratumoral Treg cell function remain to be elucidated. We investigated Treg cell function in a genetically engineered mouse model of lung adenocarcinoma and found that Treg cells suppressed ...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2015.08.006
更新日期:2015-09-15 00:00:00
abstract::The kinases RIPK1 and RIPK3 and the pseudo-kinase MLKL have been identified as key regulators of the necroptotic cell death pathway, although a role for MLKL within the whole animal has not yet been established. Here, we have shown that MLKL deficiency rescued the embryonic lethality caused by loss of Caspase-8 or FAD...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2016.07.016
更新日期:2016-09-20 00:00:00
abstract::Adaptive immune responses begin when naive CD4(+) T cells engage peptide+major histocompatibility complex class II and co-stimulatory molecules on antigen-presenting cells (APCs). Notch signaling can influence effector functions in differentiated CD4(+) T helper and T regulatory cells. Whether and how ligand-induced N...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2014.12.027
更新日期:2015-01-20 00:00:00
abstract::Elevated inflammation in the female genital tract is associated with increased HIV risk. Cervicovaginal bacteria modulate genital inflammation; however, their role in HIV susceptibility has not been elucidated. In a prospective cohort of young, healthy South African women, we found that individuals with diverse genita...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2016.12.013
更新日期:2017-01-17 00:00:00
abstract::Neutrophil accumulation is a hallmark of immune complex-mediated inflammatory disorders. Current models of neutrophil recruitment envision the capture of circulating neutrophils by activated endothelial cells. We now demonstrate that immobilized immune complexes alone support the rapid attachment of neutrophils, under...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(01)00150-9
更新日期:2001-06-01 00:00:00
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...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(03)00079-7
更新日期:2003-04-01 00:00:00
abstract::We have generated a site-directed transgenic (sd-tg) mouse model in which the JH locus has been replaced with a rearranged VDJ coding for the heavy chain of an anti-DNA antibody. In these mice, B cells expressing the anti-dsDNA specificity are negatively regulated. We observe a novel mechanism for B cell tolerance, re...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/1074-7613(95)90064-0
更新日期:1995-12-01 00:00:00
abstract::Invariant chain (Ii)-negative mice exhibit defects in MHC class II assembly and transport that results in reduced levels of surface class II, altered antigen presentation, and inefficient positive selection of CD4+ T cells. Many CD4+ T cells that do mature in Ii-negative mice express a cell surface phenotype consisten...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/1074-7613(95)90120-5
更新日期:1995-09-01 00:00:00
abstract::Tumors frequently subvert major histocompatibility complex class I (MHC-I) peptide presentation to evade CD8+ T cell immunosurveillance, though how this is accomplished is not always well defined. To identify the global regulatory networks controlling antigen presentation, we employed genome-wide screening in human di...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2020.11.002
更新日期:2021-01-12 00:00:00
abstract::Fibroblasts are major contributors to and regulators of inflammation and dominant producers of interleukin-6 (IL-6) in inflammatory diseases like rheumatoid arthritis. Yet, compared to leukocytes, the regulation of inflammatory pathways in fibroblasts is largely unknown. Here, we report that analyses of genes coordina...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2017.01.004
更新日期:2017-02-21 00:00:00
abstract::Lentiviral Nef increases T cell signaling activity, but the molecular nature of the stimulus involved is incompletely described. We explored CD4 T cell lipid raft composition in the presence and absence of Nef. Here, the E2 ubiquitin-conjugating enzyme UbcH7, which acts in conjunction with c-Cbl, is absent from lipid ...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2005.11.003
更新日期:2005-12-01 00:00:00
abstract::T lymphocyte receptor CTLA-4 binds costimulatory molecules CD80 (B7-1) and CD86 (B7-2) with high avidity and negatively regulates T cell activation. CTLA-4 functions at the cell surface, yet is primarily localized in intracellular vesicles. Here, we demonstrate cycling of CTLA-4 between intracellular stores and the ce...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80480-x
更新日期:1996-06-01 00:00:00
abstract::Regulatory T cell-mediated dominant tolerance has been demonstrated to play an important role in the prevention of autoimmunity. Here, we present data arguing that the forkhead transcription factor Foxp3 acts as the regulatory T cell lineage specification factor and mediator of the genetic mechanism of dominant tolera...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2005.01.016
更新日期:2005-03-01 00:00:00
abstract::B cell subsets expressing the transcription factor T-bet are associated with humoral immune responses and autoimmunity. Here, we examined the anatomic distribution, clonal relationships, and functional properties of T-bet+ and T-bet- memory B cells (MBCs) in the context of the influenza-specific immune response. In mi...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2020.03.020
更新日期:2020-05-19 00:00:00
abstract::In this issue of Immunity, it is found that the downregulation of Pax-5 during antigen-dependent-terminal differentiation results in a substantial loss of B cell identity and the transition to a plasma cell state. ...
journal_title:Immunity
pub_type: 评论,杂志文章
doi:10.1016/j.immuni.2006.03.005
更新日期:2006-03-01 00:00:00
abstract::The Ikaros gene family encodes zinc finger DNA-binding proteins essential for lineage determination and control of proliferation in the lymphoid system. Here, we report that, in the nucleus of a T cell, a major fraction of Ikaros and Aiolos proteins associate with the DNA-dependent ATPase Mi-2 and histone deacetylases...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80034-5
更新日期:1999-03-01 00:00:00
abstract::Fas receptor-induced apoptosis plays critical roles in immune homeostasis. However, most of the signal transduction events distal to Fas ligation have not been elucidated. Here, we show that Ras is activated following ligation of Fas on lymphoid lines. The activation of Ras is a critical component of this apoptotic pa...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/1074-7613(95)90142-6
更新日期:1995-04-01 00:00:00
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...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2005.01.006
更新日期:2005-02-01 00:00:00
abstract::Cytokine signaling via a restricted number of Jak-Stat pathways positively and negatively regulates all cell types involved in the initiation, propagation, and resolution of inflammation. Here, we focus on Jak-Stat signaling in three major cell types involved in inflammatory responses: T cells, neutrophils, and macrop...
journal_title:Immunity
pub_type: 杂志文章,评审
doi:10.1016/j.immuni.2008.03.002
更新日期:2008-04-01 00:00:00
abstract::In comparison to murine dendritic cells (DCs), less is known about the function of human DCs in tissues. Here, we analyzed, by using lung tissues from humans and humanized mice, the role of human CD1c(+) and CD141(+) DCs in determining the type of CD8(+) T cell immunity generated to live-attenuated influenza virus (LA...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2013.03.004
更新日期:2013-04-18 00:00:00
abstract::Among 631 substitutions present in 90 nurse shark immunoglobulin light chain somatic mutants, 338 constitute 2-4 bp stretches of adjacent changes. An absence of mutations in perinatal sequences and the bias for one mutating V gene in adults suggest that the diversification is antigen dependent. The substitutions share...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(02)00300-x
更新日期:2002-04-01 00:00:00
abstract::The identification of specific genetic loci that contribute to inflammatory and autoimmune diseases has proved difficult due to the contribution of multiple interacting genes, the inherent genetic heterogeneity present in human populations, and a lack of new mouse mutants. By using N-ethyl-N-nitrosourea (ENU) mutagene...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2005.01.018
更新日期:2005-04-01 00:00:00
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...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80186-7
更新日期:2000-03-01 00:00:00
abstract::The thymic medulla provides a specialized microenvironment for the negative selection of T cells, with the presence of autoimmune regulator (Aire)-expressing medullary thymic epithelial cells (mTECs) during the embryonic-neonatal period being both necessary and sufficient to establish long-lasting tolerance. Here we s...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2012.01.016
更新日期:2012-03-23 00:00:00
abstract::Antigen presentation and microbial killing are critical arms of host defense that depend upon cargo trafficking into lysosomes. Yet, the molecular regulators of traffic into lysosomes are only partly understood. Here, using a lysosome-dependent immunological screen of a trafficking shRNA library, we identified the Arf...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2011.06.009
更新日期:2011-08-26 00:00:00
abstract::T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4+ T cell accumul...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2017.10.014
更新日期:2017-11-21 00:00:00
abstract::Clonal selection theories postulate that lymphocyte fate is regulated by antigen receptor specificity. However, lymphocyte apoptosis is induced through nonantigen-specific receptors such as Fas (CD95/APO-1) or TNFR. We define a selective TCR that controls apoptosis by Fas or TNFR stimulation. Variant ligands can deliv...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80613-5
更新日期:1998-09-01 00:00:00
abstract::The innate immune system comprises several classes of pattern recognition receptors, including Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-1-like receptors (RLRs). TLRs recognize microbes on the cell surface and in endosomes, whereas NLRs and RLRs detect microbial components in the cytosol. Here we ...
journal_title:Immunity
pub_type: 杂志文章,评审
doi:10.1016/j.immuni.2007.10.002
更新日期:2007-10-01 00:00:00