Multiple Sclerosis Suppressed in Mouse Model by Oft-Overlooked Immune System Cell Type

Multiple Sclerosis Suppressed in Mouse Model by Oft-Overlooked Immune System Cell Type

Publication date: Aug 09, 2019

Findings from the team’s studies in a mouse model of MS, along with preliminary analyses of cells from patients with MS, indicated that a subset of CD8+ T cells-a type of immune system cell that typically acts to kill infected or cancer cells-may act to suppress the pathogenic CD4+ and γδ+ T cells that promote autoimmune disease.

Their results suggest that inflammatory and suppressive immune cells work to balance each other, and that selectively activating the suppressive CD8+ T cells during autoimmune diseases may restore the balance.

He found that while the peptides did trigger some types of T cell to proliferate, there was a subset of the CD8+ T cells that didn’t respond to any of the MOG peptides.

-Although the expanded CD4+ T cells are largely specific for the myelin oligodendrocyte glycoprotein (MOG) immunogenic peptide 35-55 (MOG35-55), clonally expanded CD8+ T cells were nonresponsive to myelin peptides or proteins,” the authors wrote.

Injections of the two peptides activated the CD8+ T cells, but this reduced or even prevented disease in the mice.

-Further analyses show that these T cells represent a unique subset of regulatory CD8+ T cells that suppress MOG35-55-specific CD4+ T cell proliferation, which suggests that the induction of autoreactive CD4+ T cells in EAE triggers a counteracting wave of regulatory CD8+ T cells,” the investigators commented.

Having established the existence of the regulatory CD8+ T cells in the EAE mouse model, the next stage was to see whether equivalent cells were also produced in humans with MS. The researchers’ tests found that, similar to their observations in EAE mice, people with newly diagnosed MS also tended to have large expanded populations of single cell-derived CD8+ T cells, which hinted that that CD8+ T cells in MS patients were also being activated against a specific target.

-We show here that the simultaneous mobilization of oligoclonal T cells, seen previously in patients with celiac disease, has a parallel not only in EAE, but also to some extent in newly diagnosed patients with MS. ” Davis and team are now working to find out what these human CD8+ T cells are recognizing, and whether some of them are suppressive.

They also hope to discover whether these CD8+ T cells are involved in other autoimmune diseases.

-Most importantly, given the similarities described above in the dynamics of T cell responses in celiac disease, EAE, and MS, it seems likely that pathogenic CD4+ and γδ+ T cell responses opposed by regulatory CD8+ T cells responses may be a common phenomenon across autoimmune diseases,” they concluded.

Concepts Keywords
Antigen Autoimmune disorders
Antigens Celiac
Autoimmune Getty ImagesAutoimmune diseases
Autoimmune Disease Paralysis disorder
Autoimmune Diseases Incidence mild disease
Autoimmune Disorders Treatment diseases
Autoimmunity Severe disease
Blood MS
CD4 Previously celiac disease
CD8 Immunization
Celiac Disease Immunosuppression
Central Nervous System Medical specialties
Clonally Immunology
Crowdsourcing Branches of biology
Gluten Medicine
Glycoprotein T cell
Howard Hughes Experimental autoimmune encephalomyelitis
Immune System Myelin oligodendrocyte glycoprotein
Immune System Attack CD4
Immunization Autoimmunity
Immunogenic MHC restriction
Immunology CD4+/CD8+ ratio
Immunosuppression
Immunosuppressive
Incidence
Marion
Mark Davis
Mice
Microbiology
MOG
Multiple Sclerosis
Myelin
Nature
Oligodendrocyte
Paralysis
Pathogen
Pathogenic
Peptide
Peptides
PhD
Receptors
Saligrama
Sequencing
Small Intestine
SPs
Stanford
Suppressor
T Cell
TCRs
Tests
Titanic
United States

Semantics

Type Source Name
gene UNIPROT PTPN5
disease MESH experimental autoimmune encephalomyelitis
gene UNIPROT SEPHS1
gene UNIPROT STAB2
gene UNIPROT MOG
disease MESH paralysis
disease MESH autoimmunity
gene UNIPROT PDC
drug DRUGBANK Isoxaflutole
gene UNIPROT MARK1
disease DOID autoimmune disease
disease MESH autoimmune disease
disease DOID cancer
disease MESH cancer
disease DOID celiac disease
disease MESH celiac disease
disease MESH development
gene UNIPROT LARGE1
pathway BSID Immune System
disease DOID Multiple Sclerosis
disease MESH Multiple Sclerosis
gene UNIPROT LAT2

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