Myelin specific Th1 cells are necessary for post-traumatic protective autoimmunity

Kipnis, Jonathan; Yoles, Eti; Mizrahi, Tal; Ben-Nur, Auraham; Schwartz, Michal

doi:10.1016/s0165-5728(02)00219-9

Cited by 131 publications

(83 citation statements)

References 22 publications

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“…Recent findings in our laboratory suggest that Th1 is the T cell phenotype that is needed for immune neuroprotection (28). Another recent study showed that B cells can efficiently restimulate only Th2 cells (29).…”

Section: Discussionmentioning

confidence: 98%

Severe Immunodeficiency Has Opposite Effects on Neuronal Survival in Glutamate-Susceptible and -Resistant Mice: Adverse Effect of B Cells

Schori

Lantner

Shachar

et al. 2002

The Journal of Immunology

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The resistance of rats or mice to glutamate-induced toxicity depends on their ability to spontaneously manifest a T cell-dependent response to the insult. Survival of retinal ganglion cells (RGCs) exposed to glutamate in BALB/c SCID mice (a strain relatively resistant to glutamate toxicity) was significantly worse than in the wild type. In the susceptible C57BL/6J mouse strain, however, significantly more RGCs survived among SCID mutants than in the matched wild type. RGC survival in the SCID mutants of the two strains was similar. These results suggest 1) that immunodeficiency might be an advantage in strains incapable of spontaneously manifesting protective T cell-dependent immunity and 2) that B cells might be destructive in such cases. After exposure of RGCs to toxic glutamate concentrations in three variants of B cell-deficient C57BL/6J mice, namely muMT−/− (B cell knockout mice) and Ii−/− mice reconstituted with transgenically expressed low levels of Ii p31 isoforms (p31 mice) or Ii p41 isoforms (p41 mice), significantly more RGCs survived in these mice than in the wild type. The improved survival was diminished by replenishment of the B cell-deficient mice with B cells derived from the wild type. It thus seems that B cells have an adverse effect on neuronal recovery after injury, at least in a strain that is unable to spontaneously manifest a T cell-dependent protective mechanism. These findings have clear implications for the design of immune-based therapies for CNS injury.

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Section: Discussionmentioning

confidence: 98%

Severe Immunodeficiency Has Opposite Effects on Neuronal Survival in Glutamate-Susceptible and -Resistant Mice: Adverse Effect of B Cells

Schori

Lantner

Shachar

et al. 2002

The Journal of Immunology

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“…It was shown by our group that the same autoimmune T cells can be both supportive and destructive [41]. Accordingly, in animals that are inherently susceptible to autoimmune disease the protocol used for eliciting the T cell response critically affects the outcome.…”

Section: Discussionmentioning

confidence: 99%

“…In such susceptible strains, however, autoimmune response to CNS might not be properly expressed within the therapeutic window [42]. Moreover, in susceptible strains devoid of immune cells (SCID) and thus lacking a T cell-based regulatory mechanism, passive transfer of encephalitogenic T cells causes EAE, but is not sufficient for conferring any neuroprotection [41]. In contrast, when Treg cells are passively transferred into SCID mice [40], they can have a protective effect similar to that of encephalitogenic T cells passively transferred into the wild type [6,7].…”

Section: Discussionmentioning

confidence: 99%

Vaccination with autoantigen protects against aggregated β‐amyloid and glutamate toxicity by controlling microglia: effect of CD4⁺CD25⁺ T cells

et al. 2004

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Neurodegenerative diseases differ in etiology but are propagated similarly. We show that neuronal loss caused by intraocular injection of aggregated b-amyloid was significantly greater in immunodeficient mice than in normal mice. The neurodegeneration was attenuated or augmented by elimination or addition, respectively, of naturally occurring CD4 + CD25 + regulatory T cells (Treg). Vaccination with retina-derived antigens or with the synthetic copolymer glatiramer acetate (Copolymer-1, Cop-1), but not with b-amyloid, reduced the ocular neuronal loss. In mouse hippocampal slices, microglia encountering activated T cells overcame the cytotoxicity of aggregated b-amyloid. These findings support the concept of "protective autoimmunity", show that a given T cell-based vaccination is protective at a particular site irrespective of toxicity type, and suggest that locally activated T cells induce a microglial phenotype that helps neurons withstand the insult. Alzheimer's and other neurodegenerative diseases might be arrested or retarded by vaccination with Cop-1 or related compounds or by treatment with compounds that weaken Treg suppression.

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“…Protective autoimmunity, as defined by Schwartz et al, requires proinflammatory myelinreactive T cells (84). However, other investigators have suggested that neuroprotection is conferred by T cells that are not CNS-reactive after central and peripheral nerve injury (58; 75;153).…”

Section: Lymphocytesmentioning

confidence: 99%

Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury

Donnelly

Popovich

2008

Experimental Neurology

851

755

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Trauma to the central nervous system (CNS) triggers intraparenchymal inflammation and activation of systemic immunity with the capacity to exacerbate neuropathology and stimulate mechanisms of tissue repair. Despite our incomplete understanding of the mechanisms that control these divergent functions, immune-based therapies are becoming a therapeutic focus. This review will address the complexities and controversies of post-traumatic neuroinflammation, particularly in spinal cord. In addition, current therapies designed to target neuroinflammatory cascades will be discussed.

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Myelin specific Th1 cells are necessary for post-traumatic protective autoimmunity

Cited by 131 publications

References 22 publications

Severe Immunodeficiency Has Opposite Effects on Neuronal Survival in Glutamate-Susceptible and -Resistant Mice: Adverse Effect of B Cells

Severe Immunodeficiency Has Opposite Effects on Neuronal Survival in Glutamate-Susceptible and -Resistant Mice: Adverse Effect of B Cells

Vaccination with autoantigen protects against aggregated β‐amyloid and glutamate toxicity by controlling microglia: effect of CD4⁺CD25⁺ T cells

Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury

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Myelin specific Th1 cells are necessary for post-traumatic protective autoimmunity

Cited by 131 publications

References 22 publications

Severe Immunodeficiency Has Opposite Effects on Neuronal Survival in Glutamate-Susceptible and -Resistant Mice: Adverse Effect of B Cells

Severe Immunodeficiency Has Opposite Effects on Neuronal Survival in Glutamate-Susceptible and -Resistant Mice: Adverse Effect of B Cells

Vaccination with autoantigen protects against aggregated β‐amyloid and glutamate toxicity by controlling microglia: effect of CD4+CD25+ T cells

Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury

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Vaccination with autoantigen protects against aggregated β‐amyloid and glutamate toxicity by controlling microglia: effect of CD4⁺CD25⁺ T cells