Abstract：
:Tissue cysts, the hallmark of chronic Toxoplasma gondii infection, are predominantly located in the brain making clearance of the parasite difficult. Currently available anti-T. gondii drugs are ineffective on cysts and fail to prevent reactivation of latent toxoplasmosis. We examined whether abrogation of inhibitory signaling pathways that maintain T cells in an exhausted state can be exploited for treating T. gondii tissue cysts. By using a mouse model of chronic toxoplasmosis, we showed immune checkpoint blockade directed against the programmed death-1 (PD-1) pathway results in a significant reduction in brain cyst number (77% lower). We showed leukocyte infiltration (CD3+ T cells, CD8+ T cells, and CD11b + cells) in the leptomeninges, choroid plexus, and subependymal tissue, which are known routes of entry of immune cells into the brain, and in proximal brain parenchyma. Our study provides proof of concept for blockade of immune checkpoint inhibitors as a therapy for chronic toxoplasmosis and potentially for other brain pathogens.
journal_name
J Neuroimmunoljournal_title
Journal of neuroimmunologyauthors
Xiao J,Li Y,Yolken RH,Viscidi RPdoi
10.1016/j.jneuroim.2018.03.013subject
Has Abstractpub_date
2018-06-15 00:00:00pages
55-62eissn
0165-5728issn
1872-8421pii
S0165-5728(18)30045-6journal_volume
319pub_type
杂志文章abstract：:Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats by inoculation with myelin basic protein (MBP) and adjuvants. Rats were treated with second daily injections of saline or cyclosporin A (CsA) from the day of inoculation. Saline-treated rats had an acute episode of disease followed by clinical r...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/s0165-5728(99)00047-8
更新日期：1999-06-01 00:00:00
abstract：:We describe here the methods by which enriched populations of oligodendrocytes were isolated from adult porcine brains using Percoll density gradient centrifugation and their immunological properties analyzed by a fluorescence-activated cell sorter (FACS). The analyses by immunofluorescence microscopy and FACS indicat...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/0165-5728(86)90049-4
更新日期：1986-11-01 00:00:00
abstract：:Experimental autoimmune myasthenia gravis (EAMG), which to some extent represents an experimental counterpart of human myasthenia gravis, can be induced by inoculation of various animal species and strains with acetylcholine receptor (AChR). The oral administration of Torpedo AChR to Lewis rats prior to immunization w...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/0165-5728(93)90045-z
更新日期：1993-05-01 00:00:00
abstract：:To determine the contribution of vascular endothelial growth factor (VEGF) to cerebral edema formation in bacterial meningitis, we used a VEGF neutralizing antibody to block VEGF in rabbits, following induction of meningitis by intracisternal inoculation with 10(9) heat-killed pneumococci. At 8 h, cerebrospinal fluid ...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/j.jneuroim.2004.11.013
更新日期：2005-03-01 00:00:00
abstract：:Human sera from patients with multiple sclerosis (MS) were tested using an enzyme-linked immunosorbent assay (ELISA) method on well plates coated with various dicarboxylic acid (C4 to C10) protein conjugates. Specific immunological binding was found with an azelaic acid (AzeA, C9) conjugate. The antibody titer was hig...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/0165-5728(89)90043-x
更新日期：1989-04-01 00:00:00
abstract：:We report here identification of novel mimicry epitopes for interphotoreceptor retinoid-binding protein (IRBP) 201-216, a candidate ocular antigen that causes experimental autoimmune uveoretinitis (EAU) in A/J mice. One mimicry epitope from Ehrlichia canis (EHC), designated EHC 44-59, induced cross-reactive T cells fo...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/j.jneuroim.2013.08.006
更新日期：2013-10-15 00:00:00
abstract：:Transection of the rat facial nerve leads to an intrinsic microglial reaction in the facial nucleus. In the present study, we have examined immunocytochemically the expression of cell adhesion molecules during this process. Resting microglia constitutively expressed the LFA-1 alpha and beta chain (CD11a and CD18) in t...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/0165-5728(93)90181-w
更新日期：1993-06-01 00:00:00
abstract：:Exposure of newborn mice to Gross murine leukemia virus (GMuLV) results in persistent viral infection of the central nervous system (CNS) white matter. Animals exposed to virus as neonates showed a marked depression in GMuLV-specific B lymphocyte function as evidenced by significant decreases in adult and neonatal ant...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/0165-5728(91)90093-m
更新日期：1991-10-01 00:00:00
abstract：:A cross-reactive idiotope (CRI) has been previously described on monoclonal antibodies (mAbs) specific for encephalitogenic peptides from myelin basic protein (MBP). The anti-CRI mAb, F25F7, binds an idiotope (Id) localized to the light chains of an anti-MBP peptide 1-9 mAb, denoted F23C6, and an anti-MBP peptide 80-8...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/0165-5728(93)90254-v
更新日期：1993-07-01 00:00:00
abstract：:We compared the retinal thickness in the unaffected eyes among the following subtypes of unilateral optic neuritis (ON): multiple sclerosis (MS-ON), neuromyelitis optica spectrum disorder with anti-AQP4 autoantibody (AQP4-ON), patients with serum anti-MOG antibody (MOG-ON), and idiopathic ON. In the chronic phase, mac...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/j.jneuroim.2017.10.001
更新日期：2017-12-15 00:00:00
abstract：:Most patients with paraneoplastic encephalomyelitis/sensory neuronopathy PEM/SN have small-cell lung cancer (SCLC) and develop antibodies against neuronal-specific Hu proteins, which are abnormally expressed in the tumor. Anti-Hu reactivity is present in ~16% of SCLC patients without PEM/SN. Here we test the hypothesi...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/j.jneuroim.2009.08.014
更新日期：2009-12-10 00:00:00
abstract：:In 208 children with opsoclonus-myoclonus syndrome (OMS), CSF IgG oligoclonal bands (OCB) and 22 immunomarkers in CSF and 21 in serum/blood were measured. In 36 untreated OMS, 58% were OCB(+), whereas 55% of treated OMS were OCB(-). OCB positivity or negativity did not alter concentrations or frequencies of immunomark...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/j.jneuroim.2018.04.007
更新日期：2018-08-15 00:00:00
abstract：:Multiple sclerosis affects more women than men. The reasons for this are unknown. Previously, we have shown significant differences in women versus men in inflammatory cytokine responses to the major protein component of myelin, proteolipid protein (PLP), which is thought to be a target in MS patients. Here, using the...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/j.jneuroim.2007.10.010
更新日期：2008-01-01 00:00:00
abstract：BACKGROUND/PURPOSE:In anti-myelin associated glycoprotein (anti-MAG) neuropathies, there is evidence that anti-MAG antibodies are pathogenic but numerous studies report the absence or a weak correlation between the titers of these antibodies and disease course. In this study we assessed the relationships between MAG an...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/j.jneuroim.2019.577094
更新日期：2020-02-15 00:00:00
abstract：:Changes in mitogen-induced splenocyte proliferation and NK activity were evaluated after acute (1 h) and chronic (6 d) in vivo treatment of rats with the synthetic cannabinoid compound CP-55,940. At a dose of 0.4 mg/kg i.p. it significantly inhibited the splenocyte proliferative response to PHA and NK activity but hal...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/s0165-5728(97)00149-5
更新日期：1997-12-01 00:00:00
abstract：:Complement-dependent disruption of motor endplate is detected in anti-acetylcholine receptor (AChR) antibody-positive myasthenia gravis (MG). We measured serum AChR α1 subunit protein levels, which may be associated with neuromuscular damage, in 55 patients with MG (47 were seropositive and 8 were negative) and in 20 ...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/j.jneuroim.2019.577125
更新日期：2020-02-15 00:00:00
abstract：:The expression of interleukin-1 beta (IL-1beta) mRNA was compared in the brain of inflammatory susceptible LEW/N and resistant F344/N rats at 3, 6, and 12 h after peripheral administration of lipopolysaccharide (LPS) or saline. No differences between strains were observed in the circumventricular organs (CVOs) and cho...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/s0165-5728(03)00171-1
更新日期：2003-07-01 00:00:00
abstract：:Human cytomegalovirus (CMV) infection is asymptomatic in immunocompetent individuals. However, it can lead to disease in immunodeficient population. Little is known of the mechanisms underlying the pathogenicity of the virus. We investigated the impact of CMV infection on mouse nervous system. Peripheral nerves but no...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/j.jneuroim.2019.577017
更新日期：2019-10-15 00:00:00
abstract：:Unfractionated cytokines have been shown to induce in vitro proliferation of neonatal rat Schwann cells but the nature of the mitogen(s) is not known. A mixture of rabbit antibodies specific for recombinant interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) inhibited Schwann cell proliferation induced...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/0165-5728(91)90018-3
更新日期：1991-02-01 00:00:00
abstract：:Sudden hearing loss may occur in rare cases of relapsing-remitting multiple sclerosis (RRMS). There have also been reports of idiopathic sudden sensorineural hearing loss (SNHL) in patients with neuromyelitis optica spectrum disorders (NMOSD), but the frequency of such cases is unclear. We conducted a retrospective an...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/j.jneuroim.2016.06.004
更新日期：2016-09-15 00:00:00
abstract：:Lewis (LEW) and DA rats are highly susceptible to experimental autoimmune encephalomyelitis (EAE) induced with guinea pig myelin basic protein (MBP), but respond to different epitopes. The dominant epitope for LEW rats is MBP73-86, and disease is mediated primarily by Vbeta8.2 Th1 cells. DA rats lack conventional Vbet...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/s0165-5728(01)00244-2
更新日期：2001-03-01 00:00:00
abstract：:Only few reports are available on the epitope specificity of anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in multiple sclerosis (MS). In the present study we provide a precise characterization of the epitope specificity of serum antibodies directed against the extracellular domain of MOG, including IgG, I...
journal_title：Journal of neuroimmunology
pub_type： 临床试验,杂志文章
doi：10.1016/j.jneuroim.2006.01.012
更新日期：2006-05-01 00:00:00
abstract：:To assess whether TNF-alpha causes inflammatory demyelination or axonal degeneration, we injected into rat sciatic nerve saline, 100 U and 1000 U of rhTNF-alpha and studied the electrophysiological and pathological effects. At day 1 electrophysiology showed a slight reduction of proximal compound muscle action potenti...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/s0165-5728(98)00229-x
更新日期：1999-02-01 00:00:00
abstract：:Two synthetic peripheral nerve myelin P0 protein peptides, an immunodominant (amino acids 180-199) and a cryptic (amino acids 56-71) one, induced an acute or chronic course of experimental autoimmune neuritis (EAN) in Lewis rats, when given at low dose (50-100 microg/rat) or high dose (250 microg/rat), respectively. C...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/s0165-5728(01)00245-4
更新日期：2001-03-01 00:00:00
abstract：:Serum levels of immunoreactive interleukin-2 (IL-2) were determined at monthly intervals from a group of placebo- and drug-treated chronic progressive multiple sclerosis patients before and during a cyclosporine A therapeutic trial. Significantly elevated levels of the lymphokine in active patients confirmed earlier s...
journal_title：Journal of neuroimmunology
pub_type： 临床试验,杂志文章
doi：10.1016/0165-5728(90)90036-m
更新日期：1990-06-01 00:00:00
abstract：:The interaction between lymphocytes and brain endothelium is a central pathogenetic event in CNS autoimmunity and, thus, represents an important focus of investigation. Chemokine binding through specific G protein-coupled receptors (GPCRs) on lymphocyte surface activates integrins and induces inside-out signaling and ...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章,评审
doi：10.1016/j.jneuroim.2008.04.023
更新日期：2008-07-31 00:00:00
abstract：:We used immunohistochemistry to assess the role of humoral and cellular factors in endoneurial microangiopathy and epineurial vasculitis in 15 nerve biopsies of patients with axonal neuropathy and monoclonal or mixed cryoglobulinemia (CG). Deposition of immunoglobulins and cytolytic complement was detected in endoneur...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/s0165-5728(96)00191-9
更新日期：1997-03-01 00:00:00
abstract：:In this report, we have shown the expression of the complement regulatory proteins decay-accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46) and CD59 on human D54-MG astroglioma cells by several methods, including immunofluorescence, flow cytometry and Western blotting and Northern blot analysis. Th...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/0165-5728(93)90022-q
更新日期：1993-09-01 00:00:00
abstract：:We compared the expression of various interferon-gamma (IFN-gamma)-inducible mRNAs in primary rat astrocytes and microglia. Of 11 different mRNAs inducible by IFN-gamma in a macrophage cell line, RAW 264.7, only eight were induced in both types of glia, which included mRNAs encoding the transcriptional factors, IRF-1,...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/0165-5728(94)00131-7
更新日期：1995-01-01 00:00:00
abstract：:Macrophage migration inhibitory factor (MIF) is a cytokine associated with tissue damage in multiple autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis. The role of MIF in multiple sclerosis (MS) and the contribution of its polymorphisms are unknown in our population...
journal_title：Journal of neuroimmunology
pub_type： 杂志文章
doi：10.1016/j.jneuroim.2018.04.006
更新日期：2018-07-15 00:00:00
