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Myelin-specific T Cells (myelin-specific t + cell)

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Medical Sciences100%

Selected Abstracts

Activating and inhibitory Fc, receptors can differentially modulate T cell-mediated autoimmunity

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2008
Mirentxu
Abstract The molecular bases responsible for the loss of T cell tolerance to myelin antigens leading to the onset of multiple sclerosis remain obscure. It has been shown that balanced signaling through activating and inhibitory receptors is critical for the maintenance of tolerance to self antigens in autoimmune disorders. However, although Fc,R have been shown to influence experimental autoimmune encephalomyelitis (EAE) development, their role during pathogenesis remains controversial. Here we have evaluated whether relative expression of activating (Fc,RIII) and inhibitory (Fc,RIIb) Fc,R can modulate myelin-specific T cell response, as well as the susceptibility to develop EAE in mice. While Fc,RIIb,/, mice showed a significant increase in EAE severity, an Fc,RIII deficiency protected mice from disease. In addition, Fc,RIIb,/, mice showed enhanced activation of myelin-specific effector T cells, which were significantly more effective at causing EAE in adoptive transfer experiments than were T cells from wild-type mice. In contrast, Fc,RIII,/, mice showed a significantly reduced activation of myelin-specific T cells and these cells failed to adoptively transfer EAE. Consistently, increased expansion of regulatory T cells (Treg) during EAE was observed only for Fc,RIII,/, mice, which were able to suppress disease when adoptively transferred to recipient mice. These findings suggest that the balance between activating and inhibitory Fc,R signaling can contribute to the maintenance of T cell tolerance to myelin antigens and modulate EAE progression. [source]

Defining antigen-dependent stages of T cell migration from the blood to the central nervous system parenchyma

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2005
Angela
Abstract In experimental autoimmune encephalomyelitis (EAE), intravenous transfer of activated CD4+ myelin-specific T cells is sufficient to induce disease. Transferred T cells access the CNS parenchyma by trafficking across the blood brain barrier (BBB) vascular endothelium into the perivascular space, and then across the glial limitans that is made up of astrocytes and microglia. Flow cytometry analysis of cells isolated from CNS tissue does not distinguish between T cell populations at the various stages of migration. In this study, we have used GK1.5 (anti-CD4) treatment along with immunohistochemistry to distinguish between populations of T cells that are associated with the vasculature, T cells that have migrated into the perivascular space, and T cells in the parenchyma. We have also re-evaluated antigen specificity requirements of T cells as they are recruited to the CNS parenchyma. Activated myelin-specific T cells are restricted to the CNS vasculature for at least 24,h post transfer. MHC class II expression on the recipient is required for cells to traffic across the CNS vascular endothelium. Further, Con A-stimulated or non-CNS-specific (ovalbumin-specific) T cells fail to migrate into the perivascular space, and only enter the CNS parenchyma when co-transferred with myelin-specific T cells. Our results indicate that Th1 populations cannot accumulate in the perivascular (subarachnoid, Virchow-Robbins) space without a CNS antigen-specific signal. [source]

Silencing Nogo-A promotes functional recovery in demyelinating disease

ANNALS OF NEUROLOGY, Issue 4 2010
Yuhong Yang MD
Objective To determine if suppressing Nogo-A, an axonal inhibitory protein, will promote functional recovery in a murine model of multiple sclerosis (MS). Methods A small interfering RNA was developed to specifically suppress Nogo-A (siRNA-NogoA). The siRNA-NogoA silencing effect was evaluated in vitro and in vivo via immunohistochemistry. The siRNA was administered intravenously in 2 models of experimental autoimmune encephalomyelitis (EAE). Axonal repair was measured by upregulation of GAP43. Enzyme-linked immunosorbent assay, flow cytometry, and 3H-thymidine incorporation were used to determine immunological changes in myelin-specific T cells in mice with EAE. Results The siRNA-NogoA suppressed Nogo-A expression in vitro and in vivo. Systemic administration of siRNA-NogoA ameliorated EAE and promoted axonal repair, as demonstrated by enhanced GAP43+ axons in the lesions. Myelin-specific T-cell proliferation and cytokine production were unchanged in the siRNA-NogoA,treated mice. Interpretation Silencing Nogo-A in EAE promotes functional recovery. The therapeutic benefit appears to be mediated by axonal growth and repair, and is not attributable to changes in the encephalitogenic capacity of the myelin-specific T cells. Silencing Nogo-A may be a therapeutic option for MS patients to prevent permanent functional deficits caused by immune-mediated axonal damage. ANN NEUROL 2010;67:498,507 [source]