CD4+ T Cells Have a Permissive Effect on Enriched Environment-Induced Hippocampus Synaptic Plasticity (original) (raw)
Related papers
Brain, behavior, and immunity, 2018
Enriched environment (EE) induces plasticity changes in the brain. Recently, CD4 T cells have been shown to be involved in brain plasticity processes. Here, we show that CD8 T cells are required for EE-induced brain plasticity in mice, as revealed by measurements of hippocampal volume, neurogenesis in the DG of the hippocampus, spinogenesis and glutamatergic synaptic function in the CA of the hippocampus. As a consequence, EE-induced behavioral benefits depend, at least in part, on CD8 T cells. In addition, we show that spleen CD8 T cells from mice housed in standard environment (SE) and EE have different properties in terms of 1) TNFα release after in vitro CD3/CD28 or PMA/Iono stimulation 2) in vitro proliferation properties 3) CD8 CD44 CD62L and CD62L T cells repartition 4) transcriptomic signature as revealed by RNA sequencing. CD8 T cells purified from the choroid plexus of SE and EE mice also exhibit different transcriptomic profiles as highlighted by single-cell mRNA sequenci...
Brain, Behavior, and Immunity, 2012
Neurogenesis is a well-characterized phenomenon within the dentate gyrus (DG) of the adult hippocampus. Environmental enrichment (EE) in rodents increases neurogenesis, enhances cognition, and promotes recovery from injury. However, little is known about the effects of EE on glia (astrocytes and microglia). Given their importance in neural repair, we predicted that EE would modulate glial phenotype and/or function within the hippocampus. Adult male rats were housed either 12 h/day in an enriched environment or in a standard home cage. Rats were injected with BrdU at 1 week, and after 7 weeks, half of the rats from each housing group were injected with lipopolysaccharide (LPS), and cytokine and chemokine expression was assessed within the periphery, hippocampus and cortex. Enriched rats had a markedly blunted pro-inflammatory response to LPS within the hippocampus. Specifically, expression of the chemokines Ccl2, Ccl3 and Cxcl2, several members of the tumor necrosis factor (TNF) family, and the pro-inflammatory cytokine IL-1b were all significantly decreased following LPS administration in EE rats compared to controls. EE did not impact the inflammatory response to LPS in the cortex. Moreover, EE significantly increased both astrocyte (GFAP+) and microglia (Iba1+) antigen expression within the DG, but not in the CA1, CA3, or cortex. Measures of neurogenesis were not impacted by EE (BrdU and DCX staining), although hippocampal BDNF mRNA was significantly increased by EE. This study demonstrates the importance of environmental factors on the function of the immune system specifically within the brain, which can have profound effects on neural function.
Nature Neuroscience, 2006
Neurogenesis is known to take place in the adult brain. This work identifies T lymphocytes and microglia as being important to the maintenance of hippocampal neurogenesis and spatial learning abilities in adulthood. Hippocampal neurogenesis induced by an enriched environment was associated with the recruitment of T cells and the activation of microglia. In immune-deficient mice, hippocampal neurogenesis was markedly impaired and could not be enhanced by environmental enrichment, but was restored and boosted by T cells recognizing a specific CNS antigen. CNS-specific T cells were also found to be required for spatial learning and memory and for the expression of brain-derived neurotrophic factor in the dentate gyrus, implying that a common immuneassociated mechanism underlies different aspects of hippocampal plasticity and cell renewal in the adult brain.
CNS-specific T cells shape brain function via the choroid plexus
Brain, Behavior, and Immunity, 2013
Adaptive immunity was repeatedly shown to play a role in maintaining lifelong brain function. Under physiological conditions, this activity was associated with CD4 + T cells specific for brain self-antigens. Nevertheless, direct interactions of T cells with the healthy neuronal parenchyma are hardly detectable. Recent studies have identified the brain's choroid plexus (CP) as an active neuro-immunological interface, enriched with CNS-specific CD4 + T cells. Strategically positioned for receiving signals from both the central nervous system (CNS) through the cerebrospinal fluid (CSF), and from the circulation through epithelium-immune cell interactions, the CP has recently been recognized as an important immunological compartment in maintaining and restoring brain homeostasis/allostasis. Here, we propose that CNS-specific T cells shape brain function via the CP, and suggest this immunological control to be lost as part of aging, in general, and immune senescence, in particular. Accordingly, the CP may serve as a novel target for immunomodulation to restore brain equilibrium. j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / y b r b i
PLoS Biology, 2010
Neurogenesis continues through the adult life of mice in the subgranular zone of the dentate gyrus in the hippocampus, but its function remains unclear. Measuring cellular proliferation in the hippocampus of 719 outbred heterogeneous stock mice revealed a highly significant correlation with the proportions of CD8+ versus CD4+ T lymphocyte subsets. This correlation reflected shared genetic loci, with the exception of the H-2Ea locus that had a dominant influence on T cell subsets but no impact on neurogenesis. Analysis of knockouts and repopulation of TCRa-deficient mice by subsets of T cells confirmed the influence of T cells on adult neurogenesis, indicating that CD4+ T cells or subpopulations thereof mediate the effect. Our results reveal an organismal impact, broader than hitherto suspected, of the natural genetic variation that controls T cell development and homeostasis.
2017
La plasticite cerebrale est une capacite remarquable des cellules du cerveau a adapter leur structure et fonction en reponse a l’experience et l’environnement. Cette plasticite cerebrale est favorisee par des conditions de vie favorables qui peuvent etre modelisees chez le rongeur par le modele de l’Environnement Enrichi (EE). L’EE consiste a mettre un grand nombre de souris dans de grandes cages comprenant de nombreux objets (nids, tunnels, roues…) qui sont changes regulierement. L’EE induit une activite physique volontaire accrue, des conditions optimales pour la stimulation des interactions sociales, du comportement exploratoire et des fonctions cognitives. L’EE exerce des effets benefiques sur les processus physiologiques au niveau de nombreux systemes (hormonal, cardiovasculaire, immunitaire…). L’EE reduit les comportements anxio-depressifs, ameliore l'apprentissage et la memorisation. Ces effets sont sous-tendus par des changements au niveau du cerveau et en particulier de...
How Does an Enriched Environment Impact Hippocampus Brain Plasticity?
The Hippocampus - Plasticity and Functions, 2018
Brain plasticity is profoundly impacted by one's living environment. The hippocampus, involved in learning and memory, is highly susceptible to plasticity. Raising rodents in an "enriched environment" (EE) increases learning and memorization aptitudes and decreases the anxiety of the animals. EE consists of a combination of running wheels for voluntary physical exercise, complex inanimate toys, nests, mazes, etc. all of which favor sensory stimulations and social enrichment. EE housing concomitantly increases proliferation and survival of neurons and glia in the dentate gyrus of the hippocampus, induces changes in neuronal morphology, modifies synaptic plasticity, and favors angiogenesis. The mechanisms underlying the effects of EE on plasticity, which have recently been investigated are reviewed here, including the role of glia, the involvement of molecular factors including neurotransmitters (glutamate), neurotrophic factors (BDNF), adipokines (leptin and adiponectin), chemokines, cytokines, and hormones (corticosteroid and thyroid hormones), and at a higher level, the various systems involved (neural networks and hormonal systems). We emphasize recent findings that demonstrate the major role of the immune system in modulating EE-induced changes to hippocampal plasticity. This process involves a variety of immune cells (including macrophages, microglia, natural killer, B-cells, and T-cells), although the mechanisms are yet to be fully elucidated.
CD 4+ T cells in the pathobiology of neurodegenerative disorders
Journal of Neuroimmunology, 2009
CD4+ T cells orchestrate innate and adaptive immunity. In the central nervous system they modulate immune responses including cell trafficking and glial neuroregulatory functions through an array of soluble molecules cell-cell interactions affecting tissue homeostasis. During disease their roles evolve to an auto-aggressive or, alternatively, protective phenotype. How such a balance is struck in the setting of neurodegenerative disorders may reflect a dichotomy between regulatory T cell, antiinflammatory and neuroprotective activities versus effector T cell inflammation and neurodegeneration. Interestingly, such roles may show commonalities amongst neurodegenerative diseases. Herein we focus on strategies to modulate such CD4+ T cell responses for therapeutic gain.
Tissue-resident memory T cells populate the human brain
Nature Communications, 2018
Most tissues are populated by tissue-resident memory T cells (TRM cells), which are adapted to their niche and appear to be indispensable for local protection against pathogens. Here we show that human white matter-derived brain CD8+ T cells can be subsetted into CD103−CD69+ and CD103+CD69+ T cells both with a phenotypic and transcription factor profile consistent with TRM cells. Specifically, CD103 expression in brain CD8+ T cells correlates with reduced expression of differentiation markers, increased expression of tissue-homing chemokine receptors, intermediate and low expression of the transcription factors T-bet and eomes, increased expression of PD-1 and CTLA-4, and low expression of cytolytic enzymes with preserved polyfunctionality upon activation. Brain CD4+ T cells also display TRM cell-associated markers but have low CD103 expression. We conclude that the human brain is surveilled by TRM cells, providing protection against neurotropic virus reactivation, whilst being under tight control of key immune checkpoint molecules.
Frontiers in Cellular Neuroscience, 2020
Environmental enrichment (EE) has been shown to modulate behavior and immunity. We recently reported that both short and long-term EE enhance baseline locomotion and alleviate depressive-like behavior, but only long-term EE affects locomotion adversely in a threatening environment and enhances anxiety-like behavior in middle-age mice. We have now investigated whether the observed changes in behavior after short-and long-term EE were associated with underlying immune changes. Hence, at the end of behavioral testing, mice were sacrificed, and brains and cervical lymph nodes were collected to investigate the differential effects of the duration of EE (short-and long-term) on the number of immunopositive glial cells in the dentate gyrus, CA1, CA2, and CA3 regions of the hippocampus and proportions of T cell subsets in the cervical lymph nodes using immunohistochemistry and flow cytometry, respectively. EE, regardless of duration, caused an increase in microglia number within the dentate gyrus, CA1 and CA3 hippocampal regions, but only long-term EE increased astrocytes number within the dentate gyrus and CA3 hippocampal regions. A significantly higher proportion of CD8 + naive T cells was observed after long-term EE vs. short-term EE. No significant differences were observed in the proportion of central memory and effector memory T cells or early activated CD25 + cells between any of the test groups. Our results suggest that EE, irrespective of duration, enhances the numbers of microglia, but long-term EE is required to modify astrocyte number and peripheral T cell proportions in middle-aged mice. Our findings provide new insights into the therapeutic effects of EE on various brain disorders, which may be at least partly mediated by glial and neuroimmune modulation.