Abstract:
:Progressive loss of dopaminergic neurons in the substantia nigra pars compacta and their terminal connections in the striatum are central features in Parkinson's disease (PD). Emerging evidence supports the notion that microglia neuroinflammatory responses speed neurodegenerative events. We demonstrated previously that this can be slowed by adoptive transfer of T cells from Copolymer-1-immunized mice administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) recipients. The cellular basis for this neuroprotective response was the CD4+ T cell population, suggesting involvement of CD4+CD25+ regulatory T cells (Tregs), cells known to suppress immune activation and maintain immune homeostasis and tolerance. We show for the first time that adoptive transfer of CD3-activated Tregs to MPTP-intoxicated mice provides greater than 90% protection of the nigrostriatal system. The response was dose-dependent and paralleled modulation of microglial responses and up-regulation of glial cell-derived neurotrophic factor (CDNF) and TGF-beta. Interestingly, that adoptive transfer of effector T cells showed no significant neuroprotective activities. Tregs were found to mediate neuroprotection through suppression of microglial responses to stimuli, including aggregated, nitrated alpha-synuclein. Moreover, Treg-mediated suppression was also operative following removal of Tregs from culture prior to stimulation. This neuroprotection was achieved through modulation of microglial oxidative stress and inflammation. As Tregs can be modulated in vivo, these data strongly support the use of such immunomodulatory strategies to treat PD.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Reynolds AD,Banerjee R,Liu J,Gendelman HE,Mosley RLdoi
10.1189/jlb.0507296subject
Has Abstractpub_date
2007-11-01 00:00:00pages
1083-94issue
5eissn
0741-5400issn
1938-3673pii
jlb.0507296journal_volume
82pub_type
杂志文章abstract::GCs are widely prescribed to treat inflammatory disorders and autoimmune and allergic diseases. Their anti-inflammatory and immunosuppressive effects may be related, in part, to their ability to control the maturation and functions of DCs. Here, we report that GCs inhibit the maturation of human CD34-DCs induced by th...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1110615
更新日期:2012-01-01 00:00:00
abstract::High mobility group box 1 (HMGB1) is one of the recently defined damage-associated molecular pattern molecules, passively released from necrotic cells and secreted by activated macrophage/monocytes. Whether cytolytic cells induce HMGB1 release from tumor cells is not known. We developed a highly sensitive method for d...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0306169
更新日期:2007-01-01 00:00:00
abstract::Maturation of cells of the mononuclear phagocyte lineage from bone marrow precursors to tissue macrophages (MAC) via circulating blood monocytes (MO) is a multistep process only partially understood. Similarly, MAC differentiation can be observed if MO are cultured in vitro. In an attempt to further characterize molec...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.60.4.540
更新日期:1996-10-01 00:00:00
abstract::Developmental delays, which impair antibacterial host defense, are present in the neutrophil system of human preterm neonates. We hypothesized that diminished production of interleukin-8 (IL-8), a neutrophil chemotactic peptide, might in part be responsible for these defects. To test this, monocytes from the blood of ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.53.4.399
更新日期:1993-04-01 00:00:00
abstract::The human endometrium is exposed to cyclical fluctuations of ovarian-derived sex steroids resulting in proliferation, differentiation (decidualization), and menstruation. An influx of leukocytes (up to 15% macrophages) occurs during the latter stages of the menstrual cycle, including menses. We believe the endometrial...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.0712327
更新日期:2013-02-01 00:00:00
abstract::The nucleosome, the basic structure of chromatin and normal product of cell apoptosis, plays a pivotal role both in the induction and the pathogenesis of systemic lupus erythematosus (SLE). Nucleosomes have been found to circulate at high levels in patients with SLE and apoptosis of lymphoid cells is increased during ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.64.6.774
更新日期:1998-12-01 00:00:00
abstract::We recently demonstrated that the arachidonate metabolite 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) is converted by a highly specific dehydrogenase in human neutrophils to 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), which is a potent stimulator of these cells. The objective of this study was to dete...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.59.6.847
更新日期:1996-06-01 00:00:00
abstract::TNF is a pleiotropic cytokine involved in a variety of inflammatory processes and immune responses. TNF effects are mediated via two distinct membrane receptors: TNFR1 and TNFR2. Investigations concerning regulation and function of TNFR2 revealed a novel TNFR2 isoform in human and mouse cells, termed icp75TNFR, with m...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1007713
更新日期:2008-07-01 00:00:00
abstract::Thimerosal is an organic mercury compound that is used as a preservative in vaccines and pharmaceutical products. Recent studies have shown a TH2-skewing effect of mercury, although the underlying mechanisms have not been identified. In this study, we investigated whether thimerosal can exercise a TH2-promoting effect...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0706467
更新日期:2007-02-01 00:00:00
abstract::Highly active antiretroviral therapy (HAART) against human immunodeficiency virus type 1 (HIV-1) infection dramatically suppresses viral load, leading to marked reductions in HIV-1 associated morbidity and mortality. However, infected cell reservoirs and low-level replication persist in the face of suppressive HAART, ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0306139
更新日期:2006-11-01 00:00:00
abstract::Human chorionic gonadotrophin (hCG) is a hormone produced during pregnancy and present at the implantation site and in the maternal blood. Pregnancy has been proposed to represent a controlled state of inflammation at an early stage at the implantation site and later, systemically extended to the maternal circulation....
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0208126
更新日期:2009-08-01 00:00:00
abstract::We have investigated the role of the purinergic P2X7 receptor in the formation of multinucleated giant cells in human monocyte/macrophage cultures stimulated with either concanavalin A or phytohemagglutinin. Macrophage fusion can be blocked by a P2X7-selective pharmacological antagonist or by a mAb directed against th...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/jlb.66.5.723
更新日期:1999-11-01 00:00:00
abstract::Alveolar macrophages from chronic obstructive pulmonary disease patients and cigarette smokers are deficient in their ability to phagocytose apoptotic bronchial epithelial cells (efferocytosis). We hypothesized that the defect is mediated via inhibition of sphingosine kinases and/or their subcellular mislocalization i...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.3A1015-471R
更新日期:2016-07-01 00:00:00
abstract::The synthesis and secretion of prostaglandins and leukotrienes by mouse peritoneal macrophages is under several regulatory controls. Arachidonic acid must first be released from phospholipid stores by the action of phospholipases. Macrophages have the capacity to deacylate arachidonic acid directly from the SN2 positi...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.35.1.1
更新日期:1984-01-01 00:00:00
abstract::Polymorphonuclear leukocytes (PMNs) are crucial for initial control of Streptococcus pneumoniae (pneumococcus) lung infection; however, as the infection progresses their persistence in the lungs becomes detrimental. Here we explored why the antimicrobial efficacy of PMNs declines over the course of infection. We found...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/JLB.4MA0120-115RR
更新日期:2020-09-01 00:00:00
abstract::Fetal alcohol spectrum disorder (FASD), which results from ethanol exposure during pregnancy, and alcohol use disorder (AUD), which includes both binge and chronic alcohol abuse, are strikingly common and costly at personal and societal levels. These disorders are associated with significant pathology, including that ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.3MR0416-171R
更新日期:2016-11-01 00:00:00
abstract::The expression of beta 2-integrins on gammadelta T cells in naïve mice or those with experimental autoimmune encephalomyelitis (EAE) remains poorly characterized. We compared beta 2-integrin expression and cytokine production between gammadelta and alphabeta T cells over the acute course of EAE. We observed that unlik...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0407263
更新日期:2008-01-01 00:00:00
abstract::To determine whether monocytes can be generated from CD34+ hematopoietic progenitors in large numbers, cord blood CD34+ cells were first expanded for 3-10 days in X-VIVO 10 medium supplemented with FCS, stem cell factor (SCF), thrombopoietin (TPO), and Flt-3 Ligand (Flt-3L), and then differentiated in IMDM medium supp...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0207117
更新日期:2007-09-01 00:00:00
abstract::In this study, we tested the effect of neutralizing Abs to different serotypes of E1-deleted Ad vectors on the immunogenicity of the homologous Ad vector or a vector derived from a heterologous serotype. Our results showed that, as expected, even low titers of passively transferred neutralizing Abs significantly reduc...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1A0813-451RR
更新日期:2014-11-01 00:00:00
abstract::Macrophages are known to be present in the murine uterus and are known to be among those cells comprising the uterine decidual response to pregnancy. The extent of macrophage involvement in the decidual response has not been documented, and there are unresolved questions regarding expression of markers normally associ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.38.2.255
更新日期:1985-08-01 00:00:00
abstract::Neutrophils are the first cells arriving at sites of tissue injury or infection to combat invading pathogens. Successful neutrophil recruitment to sites of inflammation highly depends on specific molecular mechanisms, fine-tuning the received information into signaling pathways and converting them into well-described ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.3MR0117-026RR
更新日期:2017-09-01 00:00:00
abstract::It is well established that the cytokine IL-12 and the transcription factor STAT4, an essential part of the IL-12 signaling pathway, are critical components of the Th1 differentiation process in T cells. In response to pathogenic stimuli, this process causes T cells to proliferate rapidly and secrete high amounts of t...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1A0814-375RR
更新日期:2015-10-01 00:00:00
abstract::Recombinant fusion proteins consisting of the extracellular domain of immunoregulatory proteins and the constant domain of immunoglobulin G (IgG) are a novel class of human therapeutics. IgG isoforms exert different levels of immune effector functions, such as complement lysis and antibody-dependent cell cytotoxicity ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
abstract::CD163, a monocyte and macrophage-specific surface glycoprotein, which is increased by interleukin-10 and glucocorticoids, is a scavenger receptor for hemoglobin/haptoglobin complexes. We report a rapid and highly reproducible rise in soluble CD163 in the plasma of human volunteers given intravenous lipopolysaccharide ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2002-10-01 00:00:00
abstract::Six IgG monoclonal antibodies representing the four murine IgG isotypes were active individually in ADCC to T-lymphoma targets mediated by murine macrophages and human blood K cells. The monoclonals were directed against four antigens (Thy-1.2, H-2k, Ly 2.1, Ly 9.2). None was as effective in ADCC as allo-anti-Thy-1.2 ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.35.1.131
更新日期:1984-01-01 00:00:00
abstract::MicroRNAs are short endogenous noncoding RNAs that play pivotal roles in a diverse range of cellular processes. The miR-181 family is important in T cell development, proliferation, and activation. In this study, we have identified BRK1 as a potential target of miR-181c using a dual selection functional assay and have...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/JLB.1A0817-325RR
更新日期:2018-05-01 00:00:00
abstract::Soluble mediators and inducible cell-surface and matrix-bound molecules coordinate the cascade of events giving rise to leukocyte emigration. Knowledge of the specific mechanisms underlying the attraction of cells into a local site, however, remains sketchy. In particular, it is unclear how chemoattractants cause rapi...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.58.4.438
更新日期:1995-10-01 00:00:00
abstract::Recent studies have shown that proinflammatory cytokines damage rodent neural precursor cells (NPCs), a source of self-renewing, multipotent cells that play an important role in the developing as well as adult brain. In this study, the effects of tumor necrosis factor alpha (TNF-alpha) on cytokine and chemokine produc...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0405221
更新日期:2005-12-01 00:00:00
abstract::Activation of beta2 integrins is necessary for neutrophil adhesion and full activation of neutrophil effector functions. We demonstrated previously that inhibition of protein kinase A (PKA) activity in quiescent neutrophils is sufficient to increase beta2-integrin cell surface expression, affinity, and adhesion. Thus,...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0405192
更新日期:2008-04-01 00:00:00
abstract::Structurally, the monocyte chemotactic proteins MCP-1, -2, and -3 form a subfamily of the C-C or beta-chemokines. Like other chemokines, MCPs are produced by a variety of cells on stimulation with cytokines (interleukin-1, tumor necrosis factor-alpha, interferon-gamma), bacterial and viral products or mitogens. MCP-1 ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/jlb.59.1.67
更新日期:1996-01-01 00:00:00