Central role of Th2/Tc2 lymphocytes in pattern II multiple sclerosis lesions.

Abstract:

OBJECTIVE:Multiple sclerosis (MS) is a disease of the central nervous system with marked heterogeneity in several aspects including pathological processes. Based on infiltrating immune cells, deposition of humoral factors and loss of oligodendrocytes and/or myelin proteins, four lesion patterns have been described. Pattern II is characterized by antibody and complement deposition in addition to T-cell infiltration. MS is considered a T-cell-mediated disease, but until now the study of pathogenic T cells has encountered major challenges, most importantly the limited access of brain-infiltrating T cells. Our objective was to identify, isolate, and characterize brain-infiltrating clonally expanded T cells in pattern II MS lesions. METHODS:We used next-generation sequencing to identify clonally expanded T cells in demyelinating pattern II brain autopsy lesions, subsequently isolated these as T-cell clones from autologous cerebrospinal fluid and functionally characterized them. RESULTS:We identified clonally expanded CD8(+) but also CD4(+) T cells in demyelinating pattern II lesions and for the first time were able to isolate these as live T-cell clones. The functional characterization shows that T cells releasing Th2 cytokines and able to provide B cell help dominate the T-cell infiltrate in pattern II brain lesions. INTERPRETATION:Our data provide the first functional evidence for a putative role of Th2/Tc2 cells in pattern II MS supporting the existence of this pathogenic phenotype and questioning the protective role that is generally ascribed to Th2 cells. Our observations are important to consider for future treatments of pattern II MS patients.

journal_name

Ann Clin Transl Neurol

authors

Planas R,Metz I,Ortiz Y,Vilarrasa N,Jelčić I,Salinas-Riester G,Heesen C,Brück W,Martin R,Sospedra M

doi

10.1002/acn3.218

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

875-93

issue

9

issn

2328-9503

journal_volume

2

pub_type

杂志文章
  • Dissociated multimodal hubs and seizures in temporal lobe epilepsy.

    abstract:OBJECTIVE:Brain connectivity at rest is altered in temporal lobe epilepsy (TLE), particularly in "hub" areas such as the posterior default mode network (DMN). Although both functional and anatomical connectivity are disturbed in TLE, the relationships between measures as well as to seizure frequency remain unclear. We ...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.173

    authors: Douw L,DeSalvo MN,Tanaka N,Cole AJ,Liu H,Reinsberger C,Stufflebeam SM

    更新日期:2015-04-01 00:00:00

  • Will time heal? A long-term follow-up of severe disorders of consciousness.

    abstract:OBJECTIVE:Little is known about the long-term outcome of patients with disorders of consciousness (DOCs) such as unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS). We describe the disease course of a large group of DOC patients 2-14 years after brain damage. METHODS:In 102 patients (59 UWS, 43...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.63

    authors: Steppacher I,Kaps M,Kissler J

    更新日期:2014-06-01 00:00:00

  • Neural networks associated with body composition in frontotemporal dementia.

    abstract:BACKGROUND:Frontotemporal dementia (FTD) is associated with complex changes in eating behavior and metabolism, which potentially affect disease pathogenesis and survival. It is currently not known if body composition changes and changes in fat deposition also exist in FTD, the relationship of these changes in eating be...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.50869

    authors: Ahmed RM,Landin-Romero R,Liang CT,Keogh JM,Henning E,Strikwerda-Brown C,Devenney EM,Hodges JR,Kiernan MC,Farooqi IS,Piguet O

    更新日期:2019-09-01 00:00:00

  • Cladribine to treat disease exacerbation after fingolimod discontinuation in progressive multiple sclerosis.

    abstract::Rebound disease following cessation of disease modifying treatment (DMT) has been reported in people with both relapsing and progressive multiple sclerosis (pwRMS, pwPMS) questioning strict separation between these two phenotypes. While licensed DMT is available for pwRMS to counter rebound disease, no such option exi...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.410

    authors: Alvarez-Gonzalez C,Adams A,Mathews J,Turner BP,Giovannoni G,Baker D,Schmierer K

    更新日期:2017-05-17 00:00:00

  • The role of ventriculoperitoneal shunting in patients with supratentorial glioma.

    abstract:OBJECTIVES:To assess the impact of ventriculoperitoneal (VPS) in patients with glioma. METHODS:Retrospective review of patients with grade II-IV glioma who had VPS placement from January 1995 to November 2012. RESULTS:We identified 62 patients. At time of VPS, 41 had gait disturbance, 40 cognitive impairment and 16 u...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.17

    authors: de la Fuente MI,DeAngelis LM

    更新日期:2014-01-01 00:00:00

  • Longitudinal advanced MRI case report of white matter radiation necrosis.

    abstract::Radiation necrosis mostly occurs in and near the radiation field. We used magnetic resonance imaging to study radiation-induced necrosis of atypical onset, severity, and extent following stereotactic radiosurgery for a symptomatic arteriovenous malformation. Susceptibility-sensitive imaging, T1-relaxation, myelin wate...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.704

    authors: Wiggermann V,Lapointe E,Litvin L,Graf C,Hernández-Torres E,McKenzie M,Vavasour IM,Laule C,MacMillan EL,Li DKB,Kolind SH,Rauscher A,Traboulsee AL

    更新日期:2018-12-10 00:00:00

  • Metabotropic glutamate receptor 5: a target for migraine therapy.

    abstract:INTRODUCTION:Many patients suffering from migraine gain little relief from existing treatments partly because many existing acute and preventive therapies used in migraine have been adopted from other neurologic conditions such as depression or epilepsy. Here, we present data supporting a new migraine-specific target, ...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.302

    authors: Waung MW,Akerman S,Wakefield M,Keywood C,Goadsby PJ

    更新日期:2016-07-01 00:00:00

  • A novel de novo RNF216 mutation associated with autosomal recessive Huntington-like disorder.

    abstract::Mutations in RNF216 have been found to be associated with autosomal recessive Huntington-like disorder. Here, we describe a patient with Huntington-like disorder caused by a novel de novo RNF216 mutation. The patient started to have choreatic movements of both hands, slowly progressing to head, face, and four extremit...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.51047

    authors: Chen KL,Zhao GX,Wang H,Wei L,Huang YY,Chen SD,Lin BY,Dong Q,Cui M,Yu JT

    更新日期:2020-05-01 00:00:00

  • The case of a 61-year-old man with unusual headaches.

    abstract::A 61-year-old man with past medical history significant for prediabetes, hyperlipidemia and high-grade prostate intraepithelial neoplasia presents with headaches for one month. Imaging of his brain reveals hydrocephalus and spine imaging reveals a cord lesion. These findings are discussed further in the case. ...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.51179

    authors: Yu M,Brooker S,Priyadarshini S

    更新日期:2020-12-18 00:00:00

  • Association of serum Apolipoprotein B with cerebrospinal fluid biomarkers of Alzheimer's pathology.

    abstract:OBJECTIVE:To examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1), or their ratio (ApoB/A1) were associated with early changes in cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology in elderly adults with subjective cognitive decline (SCD). METHODS:This study included 507 objectiv...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.51153

    authors: Hu H,Tan L,Bi YL,Xu W,Tan L,Shen XN,Hou XH,Ma YH,Dong Q,Yu JT

    更新日期:2020-10-01 00:00:00

  • Biomarkers for REM sleep behavior disorder in idiopathic and narcoleptic patients.

    abstract::To search for discriminating biomarkers, 30 patients with idiopathic rapid-eye-movements sleep behavior disorder (iRBD) were compared with 17 patients with RBD within narcolepsy type 1. Both groups underwent extensive examinations, including skin biopsy searching for phosphorylated α-synuclein deposits and whole-night...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.50833

    authors: Antelmi E,Pizza F,Donadio V,Filardi M,Sosero YL,Incensi A,Vandi S,Moresco M,Ferri R,Marelli S,Ferini-Strambi L,Liguori R,Plazzi G

    更新日期:2019-09-01 00:00:00

  • High-throughput sequencing of immune repertoires in multiple sclerosis.

    abstract::T cells and B cells are crucial in the initiation and maintenance of multiple sclerosis (MS), and the activation of these cells is believed to be mediated through specific recognition of antigens by the T- and B-cell receptors. The antigen receptors are highly polymorphic due to recombination (T- and B-cell receptors)...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章,评审

    doi:10.1002/acn3.295

    authors: Lossius A,Johansen JN,Vartdal F,Holmøy T

    更新日期:2016-02-25 00:00:00

  • Urate is closely linked to white matter integrity in multiple system atrophy.

    abstract:OBJECTIVE:We aimed to investigate the association of the serum urate level with cortical thickness and white matter integrity in multiple system atrophy (MSA). METHODS:We recruited 75 MSA patients and 42 controls who underwent brain MRI and measured serum urate level at baseline. Using cortical thickness and tract-bas...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.51073

    authors: Yoo HS,Chung SJ,Lee YH,Ye BS,Sohn YH,Kwon H,Lee PH

    更新日期:2020-06-01 00:00:00

  • Is seizure frequency variance a predictable quantity?

    abstract:Background:There is currently no formal method for predicting the range expected in an individual's seizure counts. Having access to such a prediction would be of benefit for developing more efficient clinical trials, but also for improving clinical care in the outpatient setting. Methods:Using three independently col...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.519

    authors: Goldenholz DM,Goldenholz SR,Moss R,French J,Lowenstein D,Kuzniecky R,Haut S,Cristofaro S,Detyniecki K,Hixson J,Karoly P,Cook M,Strashny A,Theodore WH

    更新日期:2018-01-09 00:00:00

  • Temporal association of sNfL and gad-enhancing lesions in multiple sclerosis.

    abstract:OBJECTIVE:Multiple sclerosis (MS) is an autoimmune demyelinating disorder, which is characterized by relapses and remissions. Serum neurofilament light chain (sNfL) is an emerging biomarker of disease activity but its clinical use is still limited. In this study, we aim to characterize the temporal association between ...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.51060

    authors: Rosso M,Gonzalez CT,Healy BC,Saxena S,Paul A,Bjornevik K,Kuhle J,Benkert P,Leppert D,Guttmann C,Bakshi R,Weiner HL,Chitnis T

    更新日期:2020-06-01 00:00:00

  • New phenotype of DCTN1-related spectrum: early-onset dHMN plus congenital foot deformity.

    abstract:OBJECTIVE:To describe the clinical and genetic features of two patients with different phenotypes due to various Dynactin 1 (DCTN1) gene mutations and further explore the phenotype-genotype relationship. METHODS:Patient 1 is a 23-year-old man with congenital foot deformity and life-long distal muscle weakness and atro...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.50985

    authors: Tian WT,Liu LH,Zhou HY,Zhang C,Zhan FX,Zhu ZY,Chen SD,Luan XH,Cao L

    更新日期:2020-02-01 00:00:00

  • Heritability of alpha and sensorimotor network changes in temporal lobe epilepsy.

    abstract:OBJECTIVE:Electroencephalography (EEG) features in the alpha band have been shown to differ between people with epilepsy and healthy controls. Here, in a group of patients with mesial temporal lobe epilepsy (mTLE), we seek to confirm these EEG features, and using simultaneous functional magnetic resonance imaging, we i...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.51032

    authors: Yaakub SN,Tangwiriyasakul C,Abela E,Koutroumanidis M,Elwes RDC,Barker GJ,Richardson MP

    更新日期:2020-05-01 00:00:00

  • A plasma diagnostic model of human T-cell leukemia virus-1 associated myelopathy.

    abstract:OBJECTIVE:Human T-cell leukemia virus-1 (HTLV-1) associated myelopathy/tropic spastic paraparesis (HAM/TSP) is induced by chronic inflammation in spinal cord due to HTLV-1 infection. Cerebrospinal fluid (CSF) neopterin or proviral load are clinically measured as disease grading biomarkers, however, they are not exactly...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.169

    authors: Ishihara M,Araya N,Sato T,Saichi N,Fujii R,Yamano Y,Ueda K

    更新日期:2015-03-01 00:00:00

  • Cognitive deficits in acute mild ischemic stroke and TIA and effects of rt-PA.

    abstract:Introduction:It is unknown if treatment with rt-PA in mild acute ischemic stroke (MIS) is associated with improvement in long term cognition. Methods:Forty-five patients with suspected acute mild stroke or transient ischemic attacks with NIHSS ≤6 were enrolled in a prospective cohort. Cognitive testing was performed w...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.719

    authors: Rosenbaum Halevi D,Bursaw AW,Karamchandani RR,Alderman SE,Breier JI,Vahidy FS,Aden JK,Cai C,Zhang X,Savitz SI

    更新日期:2019-01-22 00:00:00

  • Isradipine plasma pharmacokinetics and exposure-response in early Parkinson's disease.

    abstract:OBJECTIVES:Isradipine is a dihydropyridine calcium channel inhibitor that has demonstrated concentration-dependent neuroprotective effects in animal models of Parkinson's disease (PD) but failed to show efficacy in a phase 3 clinical trial. The objectives of this study were to model the plasma pharmacokinetics of israd...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.51300

    authors: Venuto CS,Yang L,Javidnia M,Oakes D,James Surmeier D,Simuni T

    更新日期:2021-01-18 00:00:00

  • De novo NSF mutations cause early infantile epileptic encephalopathy.

    abstract::N-ethylmaleimide-sensitive factor (NSF) plays a critical role in intracellular vesicle transport, which is essential for neurotransmitter release. Herein, we, for the first time, document human monogenic disease phenotype of de novo pathogenic variants in NSF, that is, epileptic encephalopathy of early infantile onset...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.50917

    authors: Suzuki H,Yoshida T,Morisada N,Uehara T,Kosaki K,Sato K,Matsubara K,Takano-Shimizu T,Takenouchi T

    更新日期:2019-11-01 00:00:00

  • Repeat expansion scanning of the NOTCH2NLC gene in patients with multiple system atrophy.

    abstract:OBJECTIVE:Trinucleotide GGC repeat expansion in the 5'UTR of the NOTCH2NLC gene has been recognized as the pathogenesis of neuronal intranuclear inclusion disease (NIID). Previous studies have described that some NIID patients showed clinical and pathological similarities with multiple system atrophy (MSA). This study ...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.51021

    authors: Fang P,Yu Y,Yao S,Chen S,Zhu M,Chen Y,Zou K,Wang L,Wang H,Xin L,Hong T,Hong D

    更新日期:2020-04-01 00:00:00

  • Anti-CD20 inhibits T cell-mediated pathology and microgliosis in the rat brain.

    abstract:OBJECTIVE:The mechanism of action of anti-B cell therapy in multiple sclerosis (MS) is not fully understood. Here, we compared the effect of anti-CD20 therapy on microglial activation in two distinct focal rat models of MS. METHODS:The effect of anti-CD20 therapy on lesion formation and extralesional microglial activa...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.94

    authors: Anthony DC,Dickens AM,Seneca N,Couch Y,Campbell S,Checa B,Kersemans V,Warren EA,Tredwell M,Sibson NR,Gouverneur V,Leppert D

    更新日期:2014-09-01 00:00:00

  • Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia.

    abstract:Objective:Previous studies have demonstrated that suppression of Nrf2 in Friedreich ataxia tissues contributes to excess oxidative stress, mitochondrial dysfunction, and reduced ATP production. Omaveloxolone, an Nrf2 activator and NF-kB suppressor, targets dysfunctional inflammatory, metabolic, and bioenergetic pathway...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/acn3.660

    authors: Lynch DR,Farmer J,Hauser L,Blair IA,Wang QQ,Mesaros C,Snyder N,Boesch S,Chin M,Delatycki MB,Giunti P,Goldsberry A,Hoyle C,McBride MG,Nachbauer W,O'Grady M,Perlman S,Subramony SH,Wilmot GR,Zesiewicz T,Meyer C

    更新日期:2018-11-10 00:00:00

  • Translocator protein in late stage Alzheimer's disease and Dementia with Lewy bodies brains.

    abstract:OBJECTIVE:Increased translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), in glial cells of the brain has been used as a neuroinflammation marker in the early and middle stages of neurodegenerative diseases, such as Alzheimer's disease (AD) and Dementia with Lewy Bodies (DLB). I...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.50837

    authors: Xu J,Sun J,Perrin RJ,Mach RH,Bales KR,Morris JC,Benzinger TLS,Holtzman DM

    更新日期:2019-08-01 00:00:00

  • Archetypal NOTCH3 mutations frequent in public exome: implications for CADASIL.

    abstract:OBJECTIVE:To determine the frequency of distinctive EGFr cysteine altering NOTCH3 mutations in the 60,706 exomes of the exome aggregation consortium (ExAC) database. METHODS:ExAC was queried for mutations distinctive for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASI...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.344

    authors: Rutten JW,Dauwerse HG,Gravesteijn G,van Belzen MJ,van der Grond J,Polke JM,Bernal-Quiros M,Lesnik Oberstein SA

    更新日期:2016-09-28 00:00:00

  • Baseline neuropsychological profiles in prion disease predict survival time.

    abstract:OBJECTIVE:Few studies have captured the neuropsychological profile of sporadic Creutzfeldt-Jakob disease (sCJD) with neuropsychological testing, and little is known about cognitive predictors of survival. We characterized baseline neuropsychological performance in sCJD and investigated associations with survival. METH...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.51115

    authors: Sundaram SE,Staffaroni AM,Walker NC,Casaletto KB,Casey M,Golubjatnikov A,Metcalf S,O'Leary K,Wong K,Benisano K,Forner S,Gonzalez Catalan M,Allen IE,Rosen HJ,Kramer JH,Geschwind MD

    更新日期:2020-09-01 00:00:00

  • Altered cortical thickness following prenatal sodium valproate exposure.

    abstract::Prenatal exposure to sodium valproate (VPA) is associated with neurodevelopmental impairments. Cortical thickness was measured in 16 children exposed prenatally to VPA and 16 controls. We found increased left inferior frontal gyrus (IFG; BA45) and left pericalcarine sulcus (BA18) thickness, an association between VPA ...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.74

    authors: Wood AG,Chen J,Barton S,Nadebaum C,Anderson VA,Catroppa C,Reutens DC,O'Brien TJ,Vajda F

    更新日期:2014-07-01 00:00:00

  • Systemic chemotherapy decreases brain glucose metabolism.

    abstract:OBJECTIVE:Cancer patients may experience neurologic adverse effects, such as alterations in neurocognitive function, as a consequence of chemotherapy. The mechanisms underlying such neurotoxic syndromes remain poorly understood. We here describe the temporal and regional effects of systemically administered platinum-ba...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.121

    authors: Horky LL,Gerbaudo VH,Zaitsev A,Plesniak W,Hainer J,Govindarajulu U,Kikinis R,Dietrich J

    更新日期:2014-10-01 00:00:00

  • Calcium-sensing receptor (CaSR) as a novel target for ischemic neuroprotection.

    abstract:OBJECT:Ischemic brain injury is the leading cause for death and long-term disability in patients who suffer cardiac arrest and embolic stroke. Excitotoxicity and subsequent Ca(2+)-overload lead to ischemic neuron death. We explore a novel mechanism concerning the role of the excitatory extracellular calcium-sensing rec...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章

    doi:10.1002/acn3.118

    authors: Kim JY,Ho H,Kim N,Liu J,Tu CL,Yenari MA,Chang W

    更新日期:2014-11-01 00:00:00