Contributions
Abstract: P760
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Immunology
Introduction: Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the Central Nervous System (CNS), probably of autoimmune origin. Autoimmune diseases can develop following pathological activation of autoreactive effector cells and/or, alternatively, after weakening of self-protective regulatory mechanisms. Most of the studies have focused on CD4+ Tregs and the role of CD8+ Tregs in MS remains largely unexplored. We previously reported the suppressive properties of rat and human CD8+CD45RCint/neg Treg cells, expressing Foxp3 and acting through IFNg, TGFb and IL34 cytokines (Guillonneau, JCI, 2007; Bézie, JCI, 2015, Bézie, Front. Immunol., 2018).
Aims: As potent regulatory T cells, we aimed to understand if a dysfunction of CD8+CD45RCint/neg T cells may contributes to the breakdown of tolerance towards CNS self-antigens in MS.
Methods: Thirty-one untreated relapsing-remitting MS patients were compared to 40 age- and gender-matched HV for phenotype, function and transcriptome analysis of CD8+CD45RCint/neg Tregs.
Results: We observed a similar frequency of blood CD8+Tregs in MS patients compared to HV and a high frequency of CD45RCneg T cells reaching the cerebrospinal fluid (CSF) in patients. In contrast the CD45RCint T cells were fewer in CSF as compared to the CD45RCneg subset. Of most interest, the IL10/IFNg-secretion featuring the most potent CD8+CD45RCint/neg Treg subset (Bézie, Front. Immunol., 2018), was significantly lower in MS patients than in HV. Furthermore, we showed by in vitro suppression assays that the extent of CD8+CD45RCint Treg suppression correlates with the severity of the disease, defined by the MS Severity Score (MSSS). Indeed, CD45RCint Tregs abitility to suppress effector T cells responses was increased in patients with a MSSS< 3 compared to HV and patients with a MSSS >3.
Conclusion: These results suggested a defective recruitment of CD8+CD45RCint Tregs in the CNS of MS patients, together with an altered suppressive ability of the cells in patients depending on the severity of the disease. Thus, CD8+CD45RCint/neg T cells might bring new insights in the pathophysiology and increasing their function may lead to new therapeutic approaches of MS.
Disclosure: Naïl Benallegue : nothing to disclose
Bryan Nicol : nothing to disclose
Séverine Bézie : nothing to disclose
Nadège Vimont : nothing to disclose
Léa Flippe : nothing to disclose
Hadrien Regue : nothing to disclose
Alexandra Garcia : nothing to disclose
David A. Laplaud : Honoraria and consulting fees from Biogen,
Sanofi-Genzyme, Bayer, Novartis, Teva, Merck-Serono, Roche and Medday.
Research supports from Biogen, Novartis, Sanofi-Genzyme, Roche and
Medday.
Carole Guillonneau : nothing to disclose
Abstract: P760
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Immunology
Introduction: Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the Central Nervous System (CNS), probably of autoimmune origin. Autoimmune diseases can develop following pathological activation of autoreactive effector cells and/or, alternatively, after weakening of self-protective regulatory mechanisms. Most of the studies have focused on CD4+ Tregs and the role of CD8+ Tregs in MS remains largely unexplored. We previously reported the suppressive properties of rat and human CD8+CD45RCint/neg Treg cells, expressing Foxp3 and acting through IFNg, TGFb and IL34 cytokines (Guillonneau, JCI, 2007; Bézie, JCI, 2015, Bézie, Front. Immunol., 2018).
Aims: As potent regulatory T cells, we aimed to understand if a dysfunction of CD8+CD45RCint/neg T cells may contributes to the breakdown of tolerance towards CNS self-antigens in MS.
Methods: Thirty-one untreated relapsing-remitting MS patients were compared to 40 age- and gender-matched HV for phenotype, function and transcriptome analysis of CD8+CD45RCint/neg Tregs.
Results: We observed a similar frequency of blood CD8+Tregs in MS patients compared to HV and a high frequency of CD45RCneg T cells reaching the cerebrospinal fluid (CSF) in patients. In contrast the CD45RCint T cells were fewer in CSF as compared to the CD45RCneg subset. Of most interest, the IL10/IFNg-secretion featuring the most potent CD8+CD45RCint/neg Treg subset (Bézie, Front. Immunol., 2018), was significantly lower in MS patients than in HV. Furthermore, we showed by in vitro suppression assays that the extent of CD8+CD45RCint Treg suppression correlates with the severity of the disease, defined by the MS Severity Score (MSSS). Indeed, CD45RCint Tregs abitility to suppress effector T cells responses was increased in patients with a MSSS< 3 compared to HV and patients with a MSSS >3.
Conclusion: These results suggested a defective recruitment of CD8+CD45RCint Tregs in the CNS of MS patients, together with an altered suppressive ability of the cells in patients depending on the severity of the disease. Thus, CD8+CD45RCint/neg T cells might bring new insights in the pathophysiology and increasing their function may lead to new therapeutic approaches of MS.
Disclosure: Naïl Benallegue : nothing to disclose
Bryan Nicol : nothing to disclose
Séverine Bézie : nothing to disclose
Nadège Vimont : nothing to disclose
Léa Flippe : nothing to disclose
Hadrien Regue : nothing to disclose
Alexandra Garcia : nothing to disclose
David A. Laplaud : Honoraria and consulting fees from Biogen,
Sanofi-Genzyme, Bayer, Novartis, Teva, Merck-Serono, Roche and Medday.
Research supports from Biogen, Novartis, Sanofi-Genzyme, Roche and
Medday.
Carole Guillonneau : nothing to disclose