دورية أكاديمية
Patients With Severe Multiple Sclerosis Exhibit Functionally Altered CD8 + Regulatory T Cells
| العنوان: | Patients With Severe Multiple Sclerosis Exhibit Functionally Altered CD8 + Regulatory T Cells |
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| المؤلفون: | Benallegue, Nail, Nicol, Bryan, Lasselin, Juliette, Bézie, Severine, Flippe, Lea, Regue, Hadrien, Vimond, Nadege, Remy, Severine, Garcia, Alexandra, Le Frère, Fabienne, Anegon, Ignacio, Laplaud, David, Guillonneau, Carole |
| المساهمون: | Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Team 2 : Cell and gene engineering in tolerance, fertility and regenerative medicine (Team 2 - U1064 Inserm - CR2TI), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Team 5 : Neuroinflammation, mechanisms, therapeutic options (NEMO) (Team 5 - U1064 Inserm - CR2TI), Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011) |
| المصدر: | ISSN: 2332-7812 ; Neurology Neuroimmunology & Neuroinflammation ; https://hal.science/hal-03852985Test ; Neurology Neuroimmunology & Neuroinflammation, 2022, 9 (6), pp.e200016. ⟨10.1212/NXI.0000000000200016⟩ ; https://www.neurology.org/doi/10.1212/NXI.0000000000200016Test. |
| بيانات النشر: | HAL CCSD American Academy of neurology |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | CD8-Positive T-Lymphocytes, Encephalomyelitis, Autoimmune, Experimental* / metabolism, Forkhead Transcription Factors / metabolism, Humans, Animals, Interferon-gamma / metabolism, Mice, Inbred C57BL, Multiple Sclerosis* / metabolism, Multiple Sclerosis, Relapsing-Remitting, T-Lymphocytes, Regulatory / metabolism, Transforming Growth Factor beta / metabolism, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Background and Objectives Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the CNS. Studies of immune dysfunction in MS have mostly focused on CD4 + Tregs, but the role of CD8 + Tregs remains largely unexplored. We previously evidenced the suppressive properties of rat and human CD8 + CD45RC low/neg Tregs from healthy individuals, expressing Forkhead box P3 (FOXP3) and acting through interferon-gamma (IFN-γ), transforming growth factor beta (TGFβ), and interleukin-34 (IL-34). secretions to regulate immune responses and control diseases such as transplant rejection. To better understand CD8 + CD45RC low/neg Tregs contribution to MS pathology, we further investigated their phenotype, function, and transcriptome in patients with MS. Methods We enrolled adults with relapsing-remitting MS and age-matched and sex-matched healthy volunteers (HVs). CD8 + T cells were segregated based on low or lack of expression of CD45RC. First, the frequency in CSF and blood, phenotype, transcriptome, and function of CD8 + CD45RC low and neg were investigated according to exacerbation status and secondarily, according to clinical severity based on the MS severity score (MSSS) in patients with nonexacerbating MS. We then induced active MOG 35-55 EAE in C57Bl/6 mice and performed adoptive transfer of fresh and expanded CD8 + CD45RC neg Tregs to assess their ability to mitigate neuroinflammation in vivo. Results Thirty-one untreated patients with relapsing-remitting MS were compared with 40 age-matched and sex-matched HVs. We demonstrated no difference of CSF CD8 + CD45RC low and CD8 + CD45RC neg proportions, but blood CD8 + CD45RC low frequency was lower in patients with MS exacerbation when compared with that in HVs. CD8 + CD45RC neg Tregs but not CD8 + CD45RC low showed higher suppressive capacities in vitro in MS patients with exacerbation than in patients without acute inflammatory attack. In vitro functional assays showed a compromised suppression capacity of CD8 + CD45RC low ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/36266052; hal-03852985; https://hal.science/hal-03852985Test; https://hal.science/hal-03852985/documentTest; https://hal.science/hal-03852985/file/NXI.0000000000200016.pdfTest; PUBMED: 36266052; PUBMEDCENTRAL: PMC9621606 |
| DOI: | 10.1212/NXI.0000000000200016 |
| الإتاحة: | https://doi.org/10.1212/NXI.0000000000200016Test https://hal.science/hal-03852985Test https://hal.science/hal-03852985/documentTest https://hal.science/hal-03852985/file/NXI.0000000000200016.pdfTest |
| حقوق: | http://creativecommons.org/licenses/by-nc-ndTest/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.22D504B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1212/NXI.0000000000200016 |
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