γδ T Cells Regulate the Extent and Duration of Inflammation in the Central Nervous System by a Fas Ligand-Dependent Mechanism

Ponomarev, Eugene D.; Dittel, Bonnie N.

doi:10.4049/jimmunol.174.8.4678

Cited by 112 publications

(84 citation statements)

References 35 publications

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“…As we previously reported for wild-type B10.PL mice, 19,21 the Thy1-YFP mice exhibited a monophasic acute disease course ( Figure 1A). The mice first showed signs of clinical disease 7 to 10 days after the adoptive transfer of the MBP-specific T cells, presenting with a weak tail or hind limb ataxia.…”

Section: Thy1-yfp Mice Exhibit a Monophasic Eae Disease Coursesupporting

confidence: 53%

T-Cell-Mediated Disruption of the Neuronal Microtubule Network

Shriver

Dittel

2006

The American Journal of Pathology

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During the course of the central nervous system autoimmune disease multiple sclerosis (MS), damage to myelin leads to neurological deficits attributable to demyelination and conduction failure. However, accumulating evidence has indicated that axonal injury is also a predictor of MS clinical disease. Using the animal model of MS, experimental autoimmune encephalomyelitis (EAE), we examined whether axonal dysfunction occurred early in disease and correlated with disease symptoms. We tracked axons during EAE by using transgenic mice that express yellow fluorescent protein (YFP) in neurons. At the onset of disease, we observed a loss of YFP fluorescence in the spinal cord in areas that coincided with immune cell infiltration, before prominent demyelination. These inflammatory lesions also exhibited evidence of axonal injury but not axonal loss. During the recovery phase of EAE, the return of YFP fluorescence occurred in parallel with the resolution of inflammation. Using in vitro cultured neurons expressing YFP, we demonstrated that encephalitogenic T cells alone directed the destabilization of microtubules within neurites , resulting in a change in the pattern of YFP fluorescence. This study provides evidence that encephalitogenic T cells directly cause reversible axonal dysfunction at the onset of neurological deficits during an acute central nervous system inflammatory attack.

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Section: Thy1-yfp Mice Exhibit a Monophasic Eae Disease Coursesupporting

confidence: 53%

T-Cell-Mediated Disruption of the Neuronal Microtubule Network

Shriver

Dittel

2006

The American Journal of Pathology

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“…Mononuclear cells were isolated from the brains of mice infected with malaria on day 7 postinfection. The brains were homogenized, and mononuclear cells were isolated using 40-70% discontinuous Percoll gradients (35). Total cell numbers were determined by counting on a hemocytometer and were analyzed by FACS.…”

Section: Methodsmentioning

confidence: 99%

Genetic susceptibility to systemic lupus erythematosus protects against cerebral malaria in mice

Waisberg¹,

Тарасенко²,

Vickers³

et al. 2010

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

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Plasmodium falciparum has exerted tremendous selective pressure on genes that improve survival in severe malarial infections. Systemic lupus erythematosus (SLE) is an autoimmune disease that is six to eight times more prevalent in women of African descent than in women of European descent. Here we provide evidence that a genetic susceptibility to SLE protects against cerebral malaria. Mice that are prone to SLE because of a deficiency in FcγRIIB or overexpression of Toll-like receptor 7 are protected from death caused by cerebral malaria. Protection appears to be by immune mechanisms that allow SLE-prone mice better to control their overall inflammatory responses to parasite infections. These findings suggest that the high prevalence of SLE in women of African descent living outside of Africa may result from the inheritance of genes that are beneficial in the immune control of cerebral malaria but that, in the absence of malaria, contribute to autoimmune disease.

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“…with 1 mg of BrdU (Sigma-Aldrich) 14 h before isolation of brain mononuclear cells (4,26). Freshly isolated mononuclear cells from each experimental group were pooled and stained with anti-CD45-PE, anti-CD11b-PE-Cy5, and anti-H-2D b -biotin combined with SAallophycocyanin-Cy7.…”

Section: Brdu Labelingmentioning

confidence: 99%

CD40 Expression by Microglial Cells Is Required for Their Completion of a Two-Step Activation Process during Central Nervous System Autoimmune Inflammation

Ponomarev

Shriver

Dittel

2006

The Journal of Immunology

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146

123

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Microglial cells are monocytic lineage cells that reside in the CNS and have the capacity to become activated during various pathological conditions. Although it was demonstrated that activation of microglial cells could be achieved in vitro by the engagement of CD40-CD40L interactions in combination with proinflammatory cytokines, the exact factors that mediate activation of microglial cells in vivo during CNS autoimmunity are ill-defined. To investigate the role of CD40 in microglial cell activation during experimental autoimmune encephalomyelitis (EAE), we used bone marrow chimera mice that allowed us to distinguish microglial cells from peripheral macrophages and render microglial cells deficient in CD40. We found that the first step of microglial cell activation was CD40-independent and occurred during EAE onset. The first step of activation consisted of microglial cell proliferation and up-regulation of the activation markers MHC class II, CD40, and CD86. At the peak of disease, microglial cells underwent a second step of activation, which was characterized by a further enhancement in activation marker expression along with a reduction in proliferation. The second step of microglial cell activation was CD40-dependent and the failure of CD40-deficient microglial cells to achieve a full level of activation during EAE was correlated with reduced expansion of encephalitogenic T cells and leukocyte infiltration in the CNS, and amelioration of clinical symptoms. Thus, our findings demonstrate that CD40 expression on microglial cells is necessary to complete their activation process during EAE, which is important for disease progression.

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γδ T Cells Regulate the Extent and Duration of Inflammation in the Central Nervous System by a Fas Ligand-Dependent Mechanism

Cited by 112 publications

References 35 publications

T-Cell-Mediated Disruption of the Neuronal Microtubule Network

T-Cell-Mediated Disruption of the Neuronal Microtubule Network

Genetic susceptibility to systemic lupus erythematosus protects against cerebral malaria in mice

CD40 Expression by Microglial Cells Is Required for Their Completion of a Two-Step Activation Process during Central Nervous System Autoimmune Inflammation

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