Dynamics of the meningeal CD4+ T-cell repertoire are defined by the cervical lymph nodes and facilitate cognitive task performance in mice

Radjavi, Ali; Smirnov, Igor; Derecki, Noel; Kipnis, Jonathan

doi:10.1038/mp.2013.79

Cited by 92 publications

(83 citation statements)

References 10 publications

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“…In adults, T cells are required for spatial learning and memory (e.g., Kipnis et al 2004;Ziv et al 2006;Radjavi et al 2013; for review, see Kipnis et al 2012). MHC class I-deficient b2m 2/2 mice have a normal distribution of g d, CD4+/CD8+, and CD4+/CD8-T cells, but both b2m 2/2 and TAP1 2/2 mice lack mature CD4-/CD8+ T cells, and are defective in CD4-/ CD8+ T cell-mediated cytotoxicity (Zijlstra et al 1990;Van Kaer et al 1992).…”

Section: Discussionmentioning

confidence: 99%

MHC class I immune proteins are critical for hippocampus-dependent memory and gate NMDAR-dependent hippocampal long-term depression

et al. 2013

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Memory impairment is a common feature of conditions that involve changes in inflammatory signaling in the brain, including traumatic brain injury, infection, neurodegenerative disorders, and normal aging. However, the causal importance of inflammatory mediators in cognitive impairments in these conditions remains unclear. Here we show that specific immune proteins, members of the major histocompatibility complex class I (MHC class I), are essential for normal hippocampus-dependent memory, and are specifically required for NMDAR-dependent forms of long-term depression (LTD) in the healthy adult hippocampus. In b2m 2/2 TAP 2/2 mice, which lack stable cell-surface expression of most MHC class I proteins, NMDAR-dependent LTD in area CA1 of adult hippocampus is abolished, while NMDAR-independent forms of potentiation, facilitation, and depression are unaffected. Altered NMDAR-dependent synaptic plasticity in the hippocampus of b2m 2/2 TAP 2/2 mice is accompanied by pervasive deficits in hippocampus-dependent memory, including contextual fear memory, object recognition memory, and social recognition memory. Thus normal MHC class I expression is essential for NMDAR-dependent hippocampal synaptic depression and hippocampus-dependent memory. These results suggest that changes in MHC class I expression could be an unexpected cause of disrupted synaptic plasticity and cognitive deficits in the aging, damaged, and diseased brain.

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Section: Discussionmentioning

confidence: 99%

MHC class I immune proteins are critical for hippocampus-dependent memory and gate NMDAR-dependent hippocampal long-term depression

et al. 2013

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“…Immune deficiency in mice is often accompanied by cognitive impairment (Kipnis et al 2004Cohen et al 2006;Ziv et al 2006;Brynskikh et al 2008;Lewitus and Schwartz 2009;Derecki et al 2010;Bailey et al 2011;Gadani et al 2012;Nautiyal et al 2012;Baruch et al 2013;Radjavi et al 2013). As with neurogenesis, replenishment of the immune system by adoptive transfer of wild-type splenocytes or by bone marrow reconstitution also improves the learning ability of SCID and nude mice in MWM, Barnes maze and radial arm water maze (Brynskikh et al 2008;Ron-Harel et al 2008;Derecki et al 2010;Bailey et al 2011).…”

Section: Brain Support By the Peripheral Immune Systemmentioning

confidence: 99%

Learning and memory … and the immune system

2013

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The nervous system and the immune system are two main regulators of homeostasis in the body. Communication between them ensures normal functioning of the organism. Immune cells and molecules are required for sculpting the circuitry and determining the activity of the nervous system. Within the parenchyma of the central nervous system (CNS), microglia constantly monitor synapses and participate in their pruning during development and possibly also throughout life. Classical inflammatory cytokines, such as interleukin (IL)-1b and tumor necrosis factor (TNF), are released during neuronal activity and play a crucial role in regulating the strength of synaptic transmission. Systemically, proper functioning of the immune system is critical for maintaining normal nervous system function. Disruption of the immune system functioning leads to impairments in cognition and in neurogenesis. In this review we provide examples of the communication between the nervous and the immune systems in the interest of normal CNS development and function.

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“…We have yet to understand precisely how T-cell activity supports brain function, but certain mechanisms may prevent detrimental inflammatory responses in the meninges (Derecki et al, 2010(Derecki et al, , 2011. Intriguingly, recent evidence indicates that in the absence of autoimmune inflammation, T cells specific to CNS antigens may be of preferential importance for brain function Radjavi et al, 2014;Ziv et al, 2006). The role of the adaptive immune system in supporting brain function also becomes apparent during aging.…”

Section: Peripheral Immunity: Ripples Of Immune Responses On Brain Homentioning

confidence: 99%

Central Nervous System: (Immunological) Ivory Tower or Not?

Marin

Kipnis

2016

Neuropsychopharmacol

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The view of the nervous system being the victim of destructive inflammation during autoimmunity, degeneration, or injury has been rapidly changing. Recent studies are supporting the idea that the immune system provides support for the nervous system at various levels. Though cell patrolling through the nervous system parenchyma is limited compared with other tissues, immune cell presence within the central nervous system (CNS; microglia), as well as around it (in the meningeal spaces and choroid plexus) has been shown to be important for brain tissue maintenance and function. This review primarily explores recent findings concerning neuroimmune interactions and their mechanisms under homeostatic conditions.

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Dynamics of the meningeal CD4+ T-cell repertoire are defined by the cervical lymph nodes and facilitate cognitive task performance in mice

Cited by 92 publications

References 10 publications

MHC class I immune proteins are critical for hippocampus-dependent memory and gate NMDAR-dependent hippocampal long-term depression

MHC class I immune proteins are critical for hippocampus-dependent memory and gate NMDAR-dependent hippocampal long-term depression

Learning and memory … and the immune system

Central Nervous System: (Immunological) Ivory Tower or Not?

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