Expanded CD8 T-cell sharing between periphery and CNS in multiple sclerosis

Marion Salou (1) , Alexandra Garcia (1) , Laure Michel (1) , Anne Gainche-Salmon (1) , Delphine Loussouarn (2) , Bryan Nicol (1) , Flora Guillot (1) , Philippe Hulin , Steven Nedellec , Daniel Baron (1, 2) , Gérard Ramstein (3) , Jean-Paul Soulillou (4, 1) , Sophie Brouard (1) , Arnaud B Nicot (5, 1) , Nicolas Degauque (1) , David A Laplaud (1, 6)

1 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
2 CHU Nantes - Centre Hospitalier Universitaire de Nantes
3 LINA - Laboratoire d'Informatique de Nantes Atlantique
4 ITUN - Institut de transplantation urologie-néphrologie
5 Immunointervention dans les allo et xénotransplantations
6 CIC Nantes - Centre d’Investigation Clinique de Nantes

Objective: In multiple sclerosis (MS), central nervous system (CNS), cerebrospinal fluid (CSF), and blood display TCR clonal expansions of CD8+ T cells. These clones have been assumed – but never demonstrated – to be similar in the three compartments. Addressing this key question is essential to infer the implication of peripheral clonally expanded CD8+ T cells in the disease. Methods: For the first time, TCR Vβ repertoire from paired blood (purified CD8+ and CD4+ T cells), CSF and CNS (22 lesions, various inflammatory and demyelination statuses) samples from three MS patients was studied using complementary determining region 3 (CDR3) spectratyping and high-throughput sequencing. In parallel, blood and CNS clonally expanded CD8+ T cells were characterized by fluorescent staining. Results: TCR Vβ repertoire analysis revealed strong sharing of predominant T-cell clones between CNS lesions, CSF, and blood CD8+ T cells. In parallel, we showed that blood oligoclonal CD8+ T cells exhibit characteristics of pathogenic cells, as they displayed a bias toward a memory phenotype in MS patients, with increased expression of CCR5, CD11a and Granzyme B (GZM-B) compared to non oligoclonal counterparts. CNS-infiltrating T cells were mainly CD8 expressing CD11a and GZM-B. Interpretation: This study highlights the predominant implication of CD8+ T cells in MS pathophysiology and demonstrates that potentially aggressive CD8+ T cells can be easily identified and characterized from blood and CSF samples.

Domaines: Neurobiologie; Immunité adaptative; Médecine humaine et pathologie

Marion Salou, Alexandra Garcia, Laure Michel, Anne Gainche-Salmon, Delphine Loussouarn, et al.. Expanded CD8 T-cell sharing between periphery and CNS in multiple sclerosis. Annals of Clinical and Translational Neurology, 2015, 2 (6), pp.609-622. ⟨10.1002/acn3.199⟩. ⟨hal-01200787⟩