Heterogeneous Inflammatory Disease Of The Nervous System

Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system (CNS) in the western world, and leads to devastating disability in young adults with only limited treatment options available so far. Early in the disease course, most patients suffer from a relapsing-remitting course characterized by reversible neurological dysfunctions, such as impaired vision, paralysis, ataxia, and sensory deficits, and bladder, bowel, and sexual dysfunction. However, this...

New Insights into Adaptive Immunity in Chronic Neuroinflammation

Brandt, Josephine Herz, and Frauke Zipp Contents 1. Introduction Multiple Sclerosis Is a Heterogeneous Inflammatory Disease of the Nervous System 2 2. Experimental Autoimmune Encephalomyelitis as 3. Current Knowledge About Induction and Perseveration of Chronic Neuroinflammation 5 3.1. General considerations 5 3.3. CD8+ T cells in neuroinflammation 3.4. B cells and antibody-mediated immune responses in chronic neuroinflammation 17 4.1. General considerations 20 4.2....

Regulation of Interferong During Innate and Adaptive Immune Responses

Schoenborn* and Christopher B. Wilson* Contents 1. Introduction 43 2. IFN-g-Producing Cells 45 2.4. CD4 T cells play multiple roles in 3. Signaling Pathways Controlling IFN-g Production 3.1. NK receptors provide a dynamic rheostat to 3.2. IL-12 is a potent activator of IFN-g production in 3.3. IL-15 and IL-2 regulate NK cell development and contribute to IFN-g production 51 3.4. TGF-b is a negative regulator of IFN-g production and NK cell development 51 4. Control of IFN-g Production...

Containment of CNS inflammation by apoptosis

Apoptosis is, on the one hand, an important mechanism for the containment and reversal of CNS inflammation, but on the other hand, it has been shown to contribute to tissue damage, which is of high significance in low-proliferating tissue such as that of the CNS. In contrast to necrosis, apoptosis represents programmed cell death with a defined process of cell degradation, induced by specific death receptor ligand systems without reactive inflammation. In chronic neuroinflammation, the research...

References

Aktas, O., Waiczies, S., Smorodchenko, A., Dorr, J., Seeger, B., Prozorovski, T., Sallach, S., Endres, M., Brocke, S., Nitsch, R., and Zipp, F. (2003). Treatment of relapsing paralysis in experimental encephalomyelitis by targeting Th1 cells through atorvastatin. J. Exp. Med. 197, 725-733. Aktas, O., Smorodchenko, A., Brocke, S., Infante-Duarte, C., Topphoff, U. S., Vogt, J., Prozorovski, T., Meier, S., Osmanova, V., Pohl, E., Bechmann, I., Nitsch, R., et al. (2005). Neuronal damage in...

Interference with lymphocyte activation

Blocking IL-2 receptor IL-2 plays a key role in T cell activation and proliferation at the site of inflammation. Daclizumab is a humanized antibody against the a-chain of the IL-2 receptor (CD25) and limits T cell expansion by blocking IL-2 signaling in T cells. Its potential in immunomodulatory therapy was proven by its treatment of acute renal rejection after transplantation (Vincenti et al., 1998). After promising results in EAE (Engelhardt et al., 1989 Hayosh and Swanborg, 1987...

CD8 T cells in neuroinflammation A neverending controversy

Neuroinflammation Model

The debate about the role of CD8+ T cells in chronic neuroinflammation was started by histopathologic studies of active and chronic MS lesions, showing inconsistent results for both numbers and distribution in MS lesions. In some patients' biopsies, large numbers of oligoclonally expanded CD8+ T cells prevailed within active demyelinating lesions (Babbe et al., 2000), while others presented with scarce, often only marginal infiltration of chronic active MS lesions by CD8+ T cells (Traugott et...

CD4 T cells play multiple roles in adaptive immunity

In contrast to CD8 T cells that are hardwired for cytolytic function and IFN-g production, CD4 T cells can adopt a variety of functional effector responses. At present, four distinct CD4 effector lineages have been described Th1, Th2, Th17, and regulatory T cells (Tregs), of which only Th1 CD4 effector T cells produce large amounts of IFN-g (Dong, 2006 Harrington et al., 2006 Murphy and Reiner, 2002 Weaver et al., 2006). The contributions of Th1 and Th2 CD4 T cells to cell-mediated or...

T cell trafficking to the CNS

Cell Extravasation

For decades, it has been known that the production of proinflammatory cytokines by CNS antigen-specific CD4+ cell clones is one of the conditions necessary to initiate neuroinflammation. Another crucial step is for the immune cells to actually reach the CNS by transmigrating from the blood into the target tissue. Generally, activated memory T lymphocytes are able to enter the CNS irrespective of their antigen specificity, whereas naive lymphocytes fail to enter the healthy CNS. T lymphoblasts...

Introduction

The canonical Th1 cytokine, interferon-y IFN-y , is critical for innate and adaptive immunity against viral and intracellular bacterial infections. In humans, genetic deficiencies in the interleukin IL -12 IL-23 IFN-y pathways that result in decreased IFN-y induction or signaling are associated with strikingly increased susceptibility to mycobacterial infections Filipe-Santos et al., 2006 . Susceptibility to what are normally weakly pathogenic mycobacterial strains is greatly increased in such...