Cytotoxic CD8+T lymphocytes expressing ALS-causing SOD1 mutant selectively trigger death of spinal motoneurons

• DOI: 10.1073/pnas.1815961116
• Publication Date: 2019-01-24T02:11:01Z
• Authors: Emmanuelle Coque; Céline Salsac; Gabriel Espinosa-...; Béla Varga; Nicolas Degauque; Marion Cadoux; Roxane Crabé; Anaïs Virenque; Claire Soulard; Julie K. Fierle; Alexandre Brodovitch; Margot Libralato; Attila G. Végh; Stéphanie Venteo; Frédérique Scamps; José Boucraut; David Laplaud; Javier Hernandez; Csilla Gergely; Thierry Vincent; Cédric Raoul
• Keywords: amyotrophic lateral sclerosis; Cell Survival; [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph]; [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology; 610; Gene Expression; Mice, Transgenic; Cell Communication; cytotoxic T lymphocytes; Lymphocyte Activation; Severity of Illness Index; Granzymes; Mice; 03 medical and health sciences; Superoxide Dismutase-1; 0302 clinical medicine; 616; Animals; QH3020 Biophysics / biofizika; fas Receptor; motoneuron; Amyotrophic Lateral Sclerosis/diagnosis; Amyotrophic Lateral Sclerosis/genetics; Amyotrophic Lateral Sclerosis/metabolism; Amyotrophic Lateral Sclerosis/physiopathology; Animals; Cell Communication/immunology; Cell Death; Cell Survival/genetics; Disease Models, Animal; Gene Expression; Granzymes/metabolism; Histocompatibility Antigens Class I/immunology; Lymphocyte Activation/immunology; Mice; Mice, Transgenic; Motor Neurons/immunology; Motor Neurons/metabolism; Mutation; Phenotype; Severity of Illness Index; Spinal Cord/cytology; Superoxide Dismutase-1/genetics; T-Lymphocytes, Cytotoxic/immunology; T-Lymphocytes, Cytotoxic/metabolism; fas Receptor/metabolism; amyotrophic lateral sclerosis; cytotoxic T lymphocytes; major histocompatibility complex I; motoneuron; neuroimmunity; Motor Neurons; Cell Death; Amyotrophic Lateral Sclerosis; Histocompatibility Antigens Class I; [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology; Biological Sciences; major histocompatibility complex; 3. Good health; neuroimmunity; Disease Models, Animal; Phenotype; Spinal Cord; Mutation; major histocompatibility complex I; neuroimmunity.; T-Lymphocytes, Cytotoxic

Significance CD8 + T lymphocytes, which are typically devoted to eliminate malignant and infected cells, have been described in the central nervous system (CNS) of patients mice with amyotrophic lateral sclerosis (ALS). However, their role ALS pathogenesis has yet be unraveled. Here, we show that ablation cells increased number surviving motoneurons. expressing ALS-causing superoxide dismutase-1 mutant protein recognize selectively kill motoneurons vitro. To exert cytotoxic function, required presentation antigen-MHC-I complex at surface Analysis cell receptor diversity supports evidence self-reactive lymphocytes infiltrate CNS function.