Stroke induces specific alteration of T memory compartment controlling auto-reactive CNS antigen-specific T cell responses

Klehmet, Juliane; Höffmann, Sarah; Walter, Gerrit; Meisel, Christian; Meisel, Andreas

doi:10.1016/j.jns.2016.06.039

Cited by 17 publications

(11 citation statements)

References 43 publications

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“…Klehmet et al ( 2016 ) recently reported that the distribution of T cells changed after stroke, coinciding with the results of our study. However, Klehmet et al ( 2016 ) also found that the naïve T cell population within CD4 + T cells and CD8 + T cells was reduced early after stroke. In contrast, our results showed that the TCM population in CD4 + T cells and CD8 + T cells increased early after stroke but decreased after the acute phase of stroke.…”

Section: Discussionsupporting

confidence: 93%

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Association Between Programed Cell Death-1 and CD4+ T Cell Alterations in Different Phases of Ischemic Stroke Patients

Zhang

et al. 2018

Front. Cell. Neurosci.

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Objective: We aimed to analyze alterations in T cell subgroups during different post-ischemic stroke (IS) phases to explore the possible mechanisms underlying stroke-induced immune depression (SIID).Methods: Sixty-four IS patients who met the entry criteria were divided into three groups: an acute phase group, a sub-acute phase group and a stable phase group. Fourteen healthy individuals were selected as normal controls. The phenotype distribution of T cells in patient peripheral blood was analyzed, and the immune checkpoint receptors programed cell death-1 (PD-1) and T cell immunoglobulin and mucin domain 3 (Tim-3) were detected in different T cell phenotypes.Results: Compared with the control group, the absolute number of CD4+ T cells and CD4+ T central memory (TCM) cells was significantly increased in the acute phase group but decreased in the sub-acute phase and stable phase groups compared with that in the acute phase group. PD-1 expression in CD4+ T cells in the stable phase group showed a significant increase compared with that in the acute phase group. The expression of PD-1 on CD4+ TCM cells and CD4+ T effector memory (TEM) cells showed significant decreases in the acute phase compared with control cells; however, in the sub-acute phase and the stable phase, PD-1 expression was significantly increased compared with that in the acute phase.Conclusions: T cell dysfunction, especially CD4+ T cell dysfunction, occurred during different IS phases. PD-1 was highly expressed in CD4+ T cells of different phenotypes after the acute phase and was associated with alterations in CD4+ T cells. Particularly, PD-1 was negatively correlated with the absolute number of TCM cells among different CD4+ T cell phenotypes, which may be one of the possible mechanisms of SIID.

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Section: Discussionsupporting

confidence: 93%

“…In contrast, our results showed that the TCM population in CD4 + T cells and CD8 + T cells increased early after stroke but decreased after the acute phase of stroke. The difference in the distribution of T cells between our study and the Klehmet et al ( 2016 ) study may be a result of differences in the time points of sample collection.…”

Section: Discussioncontrasting

confidence: 75%

Association Between Programed Cell Death-1 and CD4+ T Cell Alterations in Different Phases of Ischemic Stroke Patients

Zhang

et al. 2018

Front. Cell. Neurosci.

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“…Offner et al also found that MOG-reactive cells invaded the CNS and exacerbated stoke severity, further substantiating the idea that the cellular immune response might affect stroke outcomes ( 87 ). In contrast, Meisel et al showed that stroke-induced immunodepression might represent an adaptive mechanism that inhibited long-lasting antigen-derived brain cellular immune responses ( 88 , 89 ).…”

Section: Immunity In Strokementioning

confidence: 95%

Emerging Role of Immunity in Cerebral Small Vessel Disease

Yan

2018

Front. Immunol.

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Cerebral small vessel disease (CSVD) is one of the main causes of vascular dementia in older individuals. Apart from risk containment, efforts to prevent or treat CSVD are ineffective due to the unknown pathogenesis of the disease. CSVD, a subtype of stroke, is characterized by recurrent strokes and neurodegeneration. Blood–brain barrier (BBB) impairment, chronic inflammatory responses, and leukocyte infiltration are classical pathological features of CSVD. Understanding how BBB disruption instigates inflammatory and degenerative processes may be informative for CSVD therapy. Antigens derived from the brain are found in the peripheral blood of lacunar stroke patients, and antibodies and sensitized T cells against brain antigens are also detected in patients with leukoaraiosis. These findings suggest that antigen-specific immune responses could occur in CSVD. This review describes the neurovascular unit features of CSVD, the immune responses to specific neuronal and glial processes that may be involved in a distinct mechanism of CSVD, and the current evidence of the association between mechanisms of inflammation and interventions in CSVD. We suggest that autoimmune activity should be assessed in future studies; this knowledge would benefit the development of effective therapeutic interventions in CSVD.

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“…In our studies, myelin oligodendrocyte glycoprotein (MOG)-specific splenocytes that were transferred into severe combined immunodeficient (SCID) mice migrated into the lesioned hemisphere of the SCID recipient mice which were subjected to 60 min MCAO and 96 hrs of reperfusion (Ren et al, 2012). Recently, several studies suggested that the pathogenic role of T cells in ischemic stroke is not limited to a rapid response and could be also mediated by neuroantigen specific T cells (Klehmet et al, 2016; Miro-Mur et al, 2016; Urra et al, 2014). Moreover, breakdown of the blood brain barrier (BBB) is likely to promote leakage of neuroantigens.…”

Section: Introductionmentioning

confidence: 99%

Partial MHC class II constructs as novel immunomodulatory therapy for stroke

Benedek

Vandenbark

Alkayed

et al. 2017

Neurochemistry International

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The worldwide prevalence of stroke continues to rise despite recent successes in treating acute ischemic stroke. With limited patient eligibility and associated risk of tPA and mechanical thrombectomy, new preventive and therapeutic modalities are needed to stave the rising wave of stroke. Inflammation plays a key role in brain damage after cerebral ischemia, and novel therapies that target pro-inflammatory cells have demonstrated promise for treatment for stroke. Partial MHC class II constructs have been shown to prevent and/or reverse clinical signs of various inflammatory diseases such as experimental autoimmune encephalomyelitis, collagen-induced arthritis and experimental autoimmune uveitis, by reducing the number and frequency of activated cells in the damaged CNS. Herein, we review the use of partial MHC class II constructs as a novel treatment for ischemic stroke. These constructs have been shown to reduce infarct volume and neurological deficit in various cerebral ischemia models in young adult and aging male and female mice. In addition, partial MHC class II constructs were shown to reverse stroke-associated splenic atrophy and promote a protective M2 macrophage/microglia phenotype in the CNS which contributes to tissue repair and recovery after stroke. By addressing remaining STAIR criteria, such as efficacy in large animal models of stroke, these constructs will be prime candidates for clinical trials of acute ischemic stroke.

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Stroke induces specific alteration of T memory compartment controlling auto-reactive CNS antigen-specific T cell responses

Cited by 17 publications

References 43 publications

Association Between Programed Cell Death-1 and CD4+ T Cell Alterations in Different Phases of Ischemic Stroke Patients

Association Between Programed Cell Death-1 and CD4+ T Cell Alterations in Different Phases of Ischemic Stroke Patients

Emerging Role of Immunity in Cerebral Small Vessel Disease

Partial MHC class II constructs as novel immunomodulatory therapy for stroke

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