Adaptive Immune Responses in CNS Autoimmune Disease: Mechanisms and Therapeutic Opportunities

  title={Adaptive Immune Responses in CNS Autoimmune Disease: Mechanisms and Therapeutic Opportunities},
  author={Rhoanne C. McPherson and Stephen Anderton},
  journal={Journal of Neuroimmune Pharmacology},
The processes underlying autoimmune CNS inflammation are complex, but key roles for autoimmune lymphocytes seem inevitable, based on clinical investigations in multiple sclerosis (MS) and related diseases such as neuromyelitis optica, together with the known pathogenic activity of T cells in experimental autoimmune encephalomyelitis (EAE) models. Despite intense investigation, the details of etiopathology in these diseases have been elusive. Here we describe recent advances in the rodent models… 

Peptide immunotherapy in experimental autoimmune encephalomyelitis

The current paradigms for PIT-induced tolerance in naïve T cells are discussed and the need for better understanding of the mode of action of PIT upon memory and effector T cells that are responsible for driving/sustaining ongoing autoimmune pathology is highlighted.

Celastrol Ameliorates EAE Induction by Suppressing Pathogenic T Cell Responses in the Peripheral and Central Nervous Systems

It is demonstrated that celastrol ameliorates EAE development by suppressing pathogenic Th17 responses; this finding offers a better understanding of the role of celastromethide triterpene in Eae development as well as new proposals for clinical interventions.

Expanding Role of T Cells in Human Autoimmune Diseases of the Central Nervous System

The recent progress in profiling and assessing the functionality of autoreactive T cells in central nervous system (CNS) autoimmune disorders that are currently postulated to be primarily T cell driven is reported on.

Immune Response in Neurological Pathology: Emerging Role of Central and Peripheral Immune Crosstalk

An overview of major immune effector cells and the role of the blood-brain barrier in regard to neurological disorders is provided and targeting central-peripheral immune interactions is proposed as a potential improved therapeutic strategy to overcome failures in clinical translation.

High‐throughput sequencing of immune repertoires in multiple sclerosis

How high‐throughput sequencing has provided new knowledge by surveying the immune repertoires in MS in even greater detail and with unprecedented depth is focused on.

[Neuroinflammation: Dr Jekyll or Mr Hyde?].

The specific immune crosstalk that takes place in the CNS needs to be decoded in order to identify the best therapeutic strategies aimed at helping the CNS to restore homeostasis in problematic situations, such as in the case of neurodegenerative disorders.

Exposure to inflammatory cytokines selectively limits GM-CSF production by induced T regulatory cells

It is shown that IL‐6 and IL‐27 individually, or IL‐2 and TGF‐β in combination, can mediate the selective loss of GM‐CSF production by iTreg cells, which is a critical T‐cell derived cytokine for the induction of EAE in mice.

Serum-Based Phospho-Neurofilament-Heavy Protein as Theranostic Biomarker in Three Models of Traumatic Brain Injury: An Operation Brain Trauma Therapy Study.

It is suggested that pNF-H is a useful theranostic blood-based biomarker for TAI across different rodent TBI models and levetiracetam is supported as the most promising TBI drug candidate screened by OBTT to date.



Autoimmune T cell responses in the central nervous system

  • J. Goverman
  • Biology, Medicine
    Nature Reviews Immunology
  • 2009
This Review focuses on recent progress in delineating the pathogenic mechanisms, regulation and interplay between these different T cell subsets in CNS autoimmunity.

Disturbed regulatory T cell homeostasis in multiple sclerosis.

Antigen-specific tolerance strategies for the prevention and treatment of autoimmune disease

Recent advances in the understanding of antigen-specific therapies for the treatment of autoimmune diseases are discussed.

Peptide-based therapeutic vaccines for allergic and autoimmune diseases

Future challenges in the development of therapeutic vaccines include selection of appropriate antigens and peptides, optimization of peptide dose and route of administration and identifying strategies to induce bystander suppression.

Differential regulation of central nervous system autoimmunity by TH1 and TH17 cells

It is demonstrated that T cells that are specific for different myelin epitopes generate populations characterized by different T helper type 17 (TH17) to T helpertype 1 (TH1) ratios depending on the functional avidity of interactions between TCR and peptide-MHC complexes.

Recent developments in multiple sclerosis therapeutics

Multiple sclerosis disease-modifying therapies currently in development attempt to specifically target the underlying pathology at each stage of the disease, while avoiding frequent self-injection.

Interferon beta modulates experimental autoimmune encephalomyelitis by altering the pattern of cytokine secretion.

The results indicated that rmIFN beta reduced the disease activity with an I.P. dosage of 10,000 U/day every other day, and successfully treated EAE mice revealed reduced amounts of IFN gamma.

Interferon-β Therapy Against EAE Is Effective Only When Development of the Disease Depends on the NLRP3 Inflammasome

It is demonstrated that signaling by IFNAR on macrophages inhibits activation of Rac1 and the generation of reactive oxygen species (ROS) through suppressor of cytokine signaling 1 (SOCS1) and suppressed the activity of the Nod-like receptor family, pyrin domain–containing 3 (NLRP3) inflammasome, which resulted in attenuated EAE pathogenicity.

A Pathogenic Role for Myelin-Specific Cd8+ T Cells in a Model for Multiple Sclerosis

It is demonstrated that myelin-specific CD8+ T cells induce severe CNS autoimmunity in mice, and data suggest that myelinated T cells could function as effector cells in the pathogenesis of MS.

IFN-γ Determines Distinct Clinical Outcomes in Autoimmune Encephalomyelitis1

It is believed that nonclassical spontaneous EAE could be a useful model for the study of some characteristics of multiple sclerosis not observed in classical EAE, such as the inflammatory responses in the brainstem and cerebellum that can cause vertigo.