CD4+ T, but not CD8+ or B, lymphocytes mediate facial motoneuron survival after facial nerve transection

Serpe, Craig J.; Coers, Susanna; Sanders, Virginia M.; Jones, Kathryn J.

doi:10.1016/s0889-1591(03)00028-x

Cited by 101 publications

(75 citation statements)

References 33 publications

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“…Thus, the present data implicate a key role of CD4-positive T lymphocytes in the maintenance and control of adult hippocampal neurogenesis under physiological brain conditions. This differential effect was consistent with reports that only CD4-positive T cells seem to have a neuroprotective effect on facial motor-neuron survival after peripheral nerve injury (34,35).…”

Section: Discussionsupporting

confidence: 92%

CD4-Positive T Lymphocytes Provide a Neuroimmunological Link in the Control of Adult Hippocampal Neurogenesis

Wolf

Steiner

Akpinarli

et al. 2009

The Journal of Immunology

280

235

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Adult hippocampal neurogenesis occurs in an exceptional permissive microenvironment. Neuroimmunological mechanisms might be prominently involved in the endogenous homeostatic principles that control baseline levels of adult neurogenesis. We show in this study that this homeostasis is partially dependent on CD4-positive T lymphocytes. Systemic depletion of CD4-positive T lymphocytes led to significantly reduced hippocampal neurogenesis, impaired reversal learning in the Morris water maze, and decreased brain-derived neurotrophic factor expression in the brain. No such effect of CD8 or B cells was observed. Repopulation of RAG2−/− mice with CD4, but not with CD8 cells again increased precursor cell proliferation. The T cells in our experiments were non-CNS specific and rarely detectable in the healthy brain. Thus, we can exclude cell-cell contacts between immune and brain cells or lymphocyte infiltration into the CNS as a prerequisite for an effect of CD4-T cells on neurogenesis. We propose that systemic CD4-T cell activity is required for maintaining cellular plasticity in the adult hippocampus and represents an evolutionary relevant communication route for the brain to respond to environmental changes.

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Section: Discussionsupporting

confidence: 92%

CD4-Positive T Lymphocytes Provide a Neuroimmunological Link in the Control of Adult Hippocampal Neurogenesis

Wolf

Steiner

Akpinarli

et al. 2009

The Journal of Immunology

280

235

View full text Add to dashboard Cite

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“…To test this hypothesis, mSOD1 G93A / CD4 Ϫ/Ϫ mice were generated and compared with their mSOD1 G93A /CD4 ϩ/Ϫ littermates, and although disease onset was not altered, disease progression in mSOD1 G93A /CD4 Ϫ/Ϫ mice was accelerated to the same extent as in mSOD1 G93A /RAG2 Ϫ/Ϫ mice. Thus, the CD4ϩ T cells that entered the spinal cord at sites of motoneuron injury appear to be neuroprotective (12,14,16), whereas the CD8ϩ T cells present at end-stage disease are possibly associated with injury.…”

Section: Discussionmentioning

confidence: 99%

CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS

Beers

Henkel

Zhao

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

418

414

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Neuroinflammation, marked by gliosis and infiltrating T cells, is a prominent pathological feature in diverse models of dominantly inherited neurodegenerative diseases. Recent evidence derived from transgenic mice ubiquitously overexpressing mutant Cu 2؉ / Zn 2؉ superoxide dismutase (mSOD1), a chronic neurodegenerative model of inherited amyotrophic lateral sclerosis (ALS), indicates that glia with either a lack of or reduction in mSOD1 expression enhance motoneuron protection and slow disease progression. However, the contribution of T cells that are present at sites of motoneuron injury in mSOD1 transgenic mice is not known. Here we show that when mSOD1 mice were bred with mice lacking functional T cells or CD4؉ T cells, motoneuron disease was accelerated, accompanied by unexpected attenuated morphological markers of gliosis, increased mRNA levels for proinflammatory cytokines and NOX2, and decreased levels of trophic factors and glial glutamate transporters. Bone marrow transplants reconstituted mice with T cells, prolonged survival, suppressed cytotoxicity, and restored glial activation. These results demonstrate for the first time in a model of chronic neurodegeneration that morphological activation of microglia and astroglia does not predict glial function, and that the presence of CD4؉ T cells provides supportive neuroprotection by modulating the trophic/cytotoxic balance of glia. These glial/T-cell interactions establish a novel target for therapeutic intervention in ALS and possibly other neurodegenerative diseases.amyotrophic lateral sclerosis ͉ astrocytes ͉ bone marrow transplant ͉ microglia ͉ superoxide dismutase

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“…Since we were only able to visualize CD4 + and CD8 + T cells by post-fixing sections with zinc fixative, and not with paraformaldehyde as was done with CD3 staining, it is also possible that differences in our staining methodology prevented us from accounting for all of the T cells in a particular section. Although Serpe et al (2003) showed by adoptive transfer that the CD4 + T cell sub-type was sufficient to prevent neuronal loss in immunodeficient mice, interactions between different T cell sub-types may be important to mediate neuroprotection following neuronal injury in immunologically intact mice.…”

Section: Discussionmentioning

confidence: 99%

Immunodeficiency impairs re-injury induced reversal of neuronal atrophy: Relation to T cell subsets and microglia

Ha¹,

Huang²,

Parikh³

et al. 2007

Experimental Neurology

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Following facial nerve resection in the mouse, a substantial number of neurons reside in an atrophied state (characterized by cell shrinkage and decreased ability to uptake Nissl stain), which can be reversed by re-injury. The mechanisms mediating the reversal of neuronal atrophy remain unclear. Although T cells have been shown to prevent neuronal loss following peripheral nerve injury, it was unknown whether T cells play a role in mediating the reversal of axotomy-induced neuronal atrophy. Thus, we used a facial nerve re-injury model to test the hypothesis that the reversal of neuronal atrophy would be impaired in recombinase activating gene-2 knockout (RAG-2 KO) mice, which lack functional T and B cells. Measures of neuronal survival were compared in the injured facial motor nucleus (FMN) of RAG-2 KO and wild-type (WT) mice that received a resection of the right facial nerve followed by re-injury of the same nerve 10 weeks later ("chronic resection + re-injury") or a resection of the right facial nerve followed by sham re-injury of the same nerve 10 weeks later ("chronic resection + sham"). We recently demonstrated that prior exposure to neuronal injury elicited a marked increase in T cell trafficking indicative of a T cell memory response when the contralateral FMN was injured later in adulthood. We examined if such a T cell memory response would also occur in the current re-injury model. RAG-2 KO mice showed no reversal of neuronal atrophy whereas WT mice showed a robust response. The reversal of atrophy in WT mice was not accompanied by a T cell memory response. Although the number of CD4 + and CD8 + T cells in the injured FMN did not differ from each other, double-negative T cells appear to be recruited in response to neuronal injury. Re-injury did not result in increased expression of MHC2 by microglia. Our findings suggest that T cells may be involved in reversing the axotomy-induced atrophy of injured neurons.

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CD4+ T, but not CD8+ or B, lymphocytes mediate facial motoneuron survival after facial nerve transection

Cited by 101 publications

References 33 publications

CD4-Positive T Lymphocytes Provide a Neuroimmunological Link in the Control of Adult Hippocampal Neurogenesis

CD4-Positive T Lymphocytes Provide a Neuroimmunological Link in the Control of Adult Hippocampal Neurogenesis

CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS

Immunodeficiency impairs re-injury induced reversal of neuronal atrophy: Relation to T cell subsets and microglia

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