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Published on: June 22, 2016
Patients With Severe Multiple Sclerosis Exhibit Functionally Altered CD8+ Regulatory T Cells
Nail Benallegue1, Bryan Nicol1, Juliette Lasselin1
1From the Nantes Université (N.B., B.N., J.L., S.B., L.F., H.R., N.V., S.R., A.G., I.A., D.L., C.G.), INSERM, CNRS, Center for Research in Transplantation et Translational Immunology, UMR 1064; and CHU Nantes (F.L.F.), Nantes Université, Service de Neurologie, Centre de Ressources et de Compétences Sclérose en Plaques, Nantes, France.
This study reveals a defect in CD8+CD45RClow regulatory T cells (Tregs) during multiple sclerosis (MS) relapses, impacting immune function and disease severity. These findings suggest novel therapeutic targets for MS.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- Multiple sclerosis (MS) is a chronic CNS inflammatory and demyelinating disease.
- Immune dysfunction in MS primarily focuses on CD4+ Tregs, leaving CD8+ Tregs understudied.
- Previous research indicated suppressive properties of CD8+CD45RClow/neg Tregs in healthy individuals.
Purpose of the Study:
- To investigate the phenotype, function, and transcriptome of CD8+CD45RClow/neg Tregs in MS patients.
- To understand the contribution of CD8+CD45RClow/neg Tregs to MS pathology.
- To explore potential therapeutic applications of CD8+CD45RClow/neg T cells in MS.
Main Methods:
- Enrolled adults with relapsing-remitting MS and healthy volunteers (HVs).
- Segregated CD8+ T cells based on CD45RC expression (low/neg).
- Analyzed frequency, phenotype, transcriptome, and function in CSF and blood, correlating with exacerbation status and MS severity score (MSSS).
- Induced experimental autoimmune encephalomyelitis (EAE) in mice and performed adoptive transfer of CD8+CD45RCneg Tregs.
Main Results:
- No difference in CSF CD8+CD45RClow/neg proportions between MS patients and HVs.
- Lower blood CD8+CD45RClow frequency observed in MS patients during exacerbation.
- CD8+CD45RCneg Tregs exhibited higher in vitro suppressive capacity in MS patients with exacerbation.
- Compromised suppression capacity of CD8+CD45RClow Tregs noted in non-exacerbating severe MS patients.
- Murine CD8+CD45RCneg Tregs demonstrated CNS migration and mitigated EAE in vivo.
Conclusions:
- A defect in the number and function of CD8+CD45RClow Tregs is associated with MS relapse and severity.
- CD8+CD45RClow/neg T cells offer new insights into MS pathophysiology.
- These findings suggest potential new therapeutic strategies for MS targeting CD8+CD45RClow/neg T cells.
