Production of Neurotrophins by Activated T Cells: Implications for Neuroprotective Autoimmunity

Moalem, Gila; Gdalyahu, Amos; Shani, Yael; Otten, U.; Lazarovici, Philip; Cohen, Irun R.; Schwartz, Michal

doi:10.1006/jaut.2000.0441

Cited by 308 publications

(197 citation statements)

References 74 publications

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“…Moreover, a well-controlled boost of autoimmune activity following injury increases the number of surviving neurons (43). Alternative mechanisms that may underlie T cell-mediated neuroprotection have been proposed, such as production of neurotrophic factors by T cells (44) and induction of glutamate clearance by microglia (10). However, none of these mechanisms fully address the robust neuroprotective effect induced by T cells.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Immunity: T Cell-Derived Glutamate Endows Astrocytes with a Neuroprotective Phenotype

Garg

Banerjee

Kipnis

2008

The Journal of Immunology

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A well-controlled T cell response to CNS injury may result in increased neuronal survival. However, the precise mechanism of T cell-induced neuroprotection is unknown. In this study, we report the unexpected finding that during culture of T cells, high levels of glutamate accumulate, which are efficiently cleared if T cells are cocultured with astrocytes. The T cell-derived glutamate elicits in turn, the release of neuroprotective thiols (cysteine, glutathione, and cysteinyl-glycine) and lactate from astrocytes. Media obtained from astrocytes conditioned in the presence of T cells reduce neuronal apoptosis induced by oxidative stress in primary neuronal cultures from 48 ± 14 to 9 ± 4% (p < 0.001). Inhibition of glutamate-dependent signaling during astrocyte-T cell cocultivation by a glutamate uptake inhibitor, l-aspartic acid β-hydroxamate, abolishes this neuroprotective effect. The ability of astrocytes to clear extracellular glutamate is impaired under conditions of oxidative stress. We demonstrate that T cells, via secreted cytokines, restore glutamate clearance capacity of astrocytes under oxidative conditions. Furthermore, under normoxic conditions, glutamate-buffering capacity of astrocytes is increased upon cocultivation with T cells. It is known that, following CNS injury, astrocytes can respond with beneficial or destructive effects on neurons. However, the context and signaling mechanisms for this dual astrocytic response are unknown. Our results implicate T cells as potential determinants of the context that elicits a protective role for astrocytes in the damaged CNS.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective Immunity: T Cell-Derived Glutamate Endows Astrocytes with a Neuroprotective Phenotype

Garg

Banerjee

Kipnis

2008

The Journal of Immunology

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“…Therefore, boosting the immune responses to CNS injury under certain conditions may be more beneficial than harmful to functional regeneration (58) . Implantation of activated macrophages (86) or T-lymphocyte mediated immune activity, achieved by either adoptive transfer or active immunization (87)(88)(89)(90) , enhances recovery from spinal cord injury by conferring neuroprotection or regeneration. Although the concept of neuroprotective autoimmunity is intriguing, there is no definitive mechanism that explains its efficacy.…”

Section: Therapeutic Vaccination: Good or Bad?mentioning

confidence: 99%

Inflammation and spinal cord injury: Infiltrating leukocytes as determinants of injury and repair processes

Trivedi

Olivas

Noble-Haeusslein

2006

Clinical Neuroscience Research

185

138

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The immune response that accompanies spinal cord injury contributes to both injury and reparative processes. It is this duality that is the focus of this review. Here we consider the complex cellular and molecular immune responses that lead to the infiltration of leukocytes and glial activation, promote oxidative stress and tissue damage, influence wound healing, and subsequently modulate locomotor recovery. Immunomodulatory strategies to improve outcomes are gaining momentum as ongoing research carefully dissects those pathways, which likely mediate cell injury from those, which favor recovery processes. Current therapeutic strategies address divergent approaches including early immunoblockade and vaccination with immune cells to prevent early tissue damage and support a wound-healing environment that favors plasticity. Despite these advances, there remain basic questions regarding how inflammatory cells interact in the injured spinal cord. Such questions likely arise as a result of our limited understanding of immune cell/neural interactions in a dynamic environment that culminates in progressive cell injury, demyelination, and regenerative failure.

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“…As neurotrofinas são proteínas diméricas sintetizadas e liberadas por várias células imunes (mastócitos e linfócitos) e essenciais para o desenvolvimento normal do sistema nervoso dos vertebrados 56 . A família inclui o fator de crescimento nervoso (NGF), fator neurotrófico derivado do encé-falo (BDNF), neurotrofina 3 e neurotrofina 4/5.…”

Section: Neurotrofinasunclassified

“…Neurotrophins are dimeric proteins synthesized and released by several immune cells (mast cells and lymphocytes) and they are essential for the normal development of the nervous system in vertebrates 56 . This family includes nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neutrophin 3 and neutrophin 4/5.…”

Section: Neurotrophinsmentioning

confidence: 99%

Dor neuropática: aspectos neuroquímicos

Kraychete¹,

Gozzani²,

Kraychete³

2008

Rev. Bras. Anestesiol.

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Rev Bras AnestesiolARTIGO DE REVISÃO 2008; 58: 5: 492-505 REVIEW ARTICLE RESUMO Kraychete DC, Gozzani JL, Kraychete AC -Dor Neuropática -Aspectos Neuroquímicos. JUSTIFICATIVA E OBJETIVOS:A dor neuropática é causada por lesão ou inflamação do sistema nervoso. É síndrome complexa, com mecanismos biológicos pouco esclarecidos, envolvendo teorias inflamatórias e imunes. O objetivo desta revisão foi descrever os principais fatores biológicos relacionados com a dor neuropática, associando de forma lógica as hipóteses sugeridas pela literatura. CONTEÚDO:Foram descritos os principais neuromediadores, canais iônicos e células, incluindo as do sistema imune envolvidos na excitabilidade neuronal, assim como enfatizada possível seqüência de ativação ou interação desses agentes na alteração neuroplástica decorrente da agressão ao nervo.CONCLUSÕES: Do estudo, foi possível concluir que os avanços no conhecimento da fisiopatologia da dor neuropática podem determinar novos alvos para abordagem farmacológica dessa síndrome.Unitermos: DOR: neuropática; FISIOLOGIA: neurotransmissores. SUMMARYKraychete DC, Gozzani JL, Kraychete AC -Neuropathic PainNeurochemical Aspects. BACKGROUND AND OBJECTIVES:Neuropathic pain is caused by damage or inflammation of the nervous system. It is a complex syndrome and its biological mechanisms, involving inflammatory and immunologic theories, are not clear. The objective of this review was to describe the main biologic factors associated with neuropathic pain, making a logical association between hypotheses suggested in the literature. CONTENTS:The main neuromediators, ion channels, and cells, including cells in the nervous system involved in neuronal excitation are described, and the possible activation sequence or interaction among those agents in the neoplastic change secondary to nerve damage are emphasized. CONCLUSIONS:It was possible to conclude that the advances on the knowledge of the pathophysiology of neuropathic pain can determine new pharmacologic approaches for this syndrome.

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Production of Neurotrophins by Activated T Cells: Implications for Neuroprotective Autoimmunity

Cited by 308 publications

References 74 publications

Neuroprotective Immunity: T Cell-Derived Glutamate Endows Astrocytes with a Neuroprotective Phenotype

Neuroprotective Immunity: T Cell-Derived Glutamate Endows Astrocytes with a Neuroprotective Phenotype

Inflammation and spinal cord injury: Infiltrating leukocytes as determinants of injury and repair processes

Dor neuropática: aspectos neuroquímicos

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