G. Bensimon, L. Lacomblez, and V. Meininger, A Controlled Trial of Riluzole in Amyotrophic Lateral Sclerosis, New England Journal of Medicine, vol.330, issue.9, pp.585-591, 1994.

L. H. Van-den-berg, E. Sorenson, G. Gronseth, E. A. Macklin, J. Andrews et al., Revised Airlie House consensus guidelines for design and implementation of ALS clinical trials, Neurology, vol.92, issue.14, pp.e1610-e1623, 2019.

D. Troost, J. J. Oord, and J. M. Jong, Immunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis, Neuropathology and Applied Neurobiology, vol.16, issue.5, pp.401-410, 1990.

M. E. Alexianu, M. Kozovska, and S. H. Appel, Immune reactivity in a mouse model of familial ALS correlates with disease progression, Neurology, vol.57, issue.7, pp.1282-1289, 2001.

B. Gille, M. De-schaepdryver, L. Dedeene, J. Goossens, K. G. Claeys et al., Inflammatory markers in cerebrospinal fluid: independent prognostic biomarkers in amyotrophic lateral sclerosis?, Journal of Neurology, Neurosurgery & Psychiatry, vol.90, p.jnnp-2018-319586, 2019.

J. R. Thonhoff, D. R. Beers, W. Zhao, M. Pleitez, E. P. Simpson et al., Expanded autologous regulatory T-lymphocyte infusions in ALS, Neurology - Neuroimmunology Neuroinflammation, vol.5, issue.4, p.e465, 2018.

M. C. Evans, Y. Couch, N. Sibson, and M. R. Turner, Inflammation and neurovascular changes in amyotrophic lateral sclerosis, Molecular and Cellular Neuroscience, vol.53, pp.34-41, 2013.

S. I. Khalid, L. Ampie, R. Kelly, S. S. Ladha, and C. Dardis, Immune Modulation in the Treatment of Amyotrophic Lateral Sclerosis: A Review of Clinical Trials, Frontiers in Neurology, vol.8, p.486, 2017.

K. Wing and S. Sakaguchi, Regulatory T cells exert checks and balances on self tolerance and autoimmunity, Nature Immunology, vol.11, issue.1, pp.7-13, 2009.

M. Rentzos, E. Evangelopoulos, E. Sereti, V. Zouvelou, S. Marmara et al., Alterations of T cell subsets in ALS: a systemic immune activation?, Acta Neurologica Scandinavica, vol.125, issue.4, pp.260-264, 2011.

S. Mantovani, S. Garbelli, A. Pasini, D. Alimonti, C. Perotti et al., Immune system alterations in sporadic amyotrophic lateral sclerosis patients suggest an ongoing neuroinflammatory process, Journal of Neuroimmunology, vol.210, issue.1-2, pp.73-79, 2009.

J. S. Henkel, D. R. Beers, S. Wen, A. L. Rivera, K. M. Toennis et al., Regulatory T?lymphocytes mediate amyotrophic lateral sclerosis progression and survival, EMBO Molecular Medicine, vol.5, issue.1, pp.64-79, 2012.

T. R. Malek and A. L. Bayer, Tolerance, not immunity, crucially depends on IL-2, Nature Reviews Immunology, vol.4, issue.9, pp.665-674, 2004.

E. Zorn, E. A. Nelson, M. Mohseni, F. Porcheray, H. Kim et al., IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo, Blood, vol.108, issue.5, pp.1571-1579, 2006.

Q. Tang, J. Y. Adams, C. Penaranda, K. Melli, E. Piaggio et al., Central Role of Defective Interleukin-2 Production in the Triggering of Islet Autoimmune Destruction, Immunity, vol.28, issue.5, pp.687-697, 2008.

M. Tahvildari and R. Dana, Low-Dose IL-2 Therapy in Transplantation, Autoimmunity, and Inflammatory Diseases, The Journal of Immunology, vol.203, issue.11, pp.2749-2755, 2019.

A. Hartemann, G. Bensimon, C. A. Payan, S. Jacqueminet, O. Bourron et al., Low-dose interleukin 2 in patients with type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial, The Lancet Diabetes & Endocrinology, vol.1, issue.4, pp.295-305, 2013.

B. R. Brooks, R. G. Miller, M. Swash, and T. L. Munsat, El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis, Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders, vol.1, issue.5, pp.293-299, 2000.

J. Gaiottino, N. Norgren, R. Dobson, J. Topping, A. Nissim et al., Increased Neurofilament Light Chain Blood Levels in Neurodegenerative Neurological Diseases, PLoS ONE, vol.8, issue.9, p.e75091, 2013.

M. Gisslén, R. W. Price, U. Andreasson, N. Norgren, S. Nilsson et al., Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study, EBioMedicine, vol.3, pp.135-140, 2016.

H. J. Keselman, R. Cribbie, and B. Holland, The pairwise multiple comparison multiplicity problem: An alternative approach to familywise and comparison wise Type I error control., Psychological Methods, vol.4, issue.1, pp.58-69, 1999.

J. R. Thonhoff, E. P. Simpson, and S. H. Appel, Neuroinflammatory mechanisms in amyotrophic lateral sclerosis pathogenesis, Current Opinion in Neurology, vol.31, issue.5, pp.635-639, 2018.

T. O?connor, L. Borsig, and M. Heikenwalder, CCL2-CCR2 Signaling in Disease Pathogenesis, Endocrine, Metabolic & Immune Disorders-Drug Targets, vol.15, issue.2, pp.105-118, 2015.

T. Nagata, I. Nagano, M. Shiote, H. Narai, T. Murakami et al., Elevation of MCP-1 and MCP-1/VEGF ratio in cerebrospinal fluid of amyotrophic lateral sclerosis patients, Neurological Research, vol.29, issue.8, pp.772-776, 2007.

S. Mammana, P. Fagone, E. Cavalli, M. Basile, M. Petralia et al., The Role of Macrophages in Neuroinflammatory and Neurodegenerative Pathways of Alzheimer?s Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis: Pathogenetic Cellular Effectors and Potential Therapeutic Targets, International Journal of Molecular Sciences, vol.19, issue.3, p.831, 2018.

B. Liao, W. Zhao, D. R. Beers, J. S. Henkel, and S. H. Appel, Transformation from a neuroprotective to a neurotoxic microglial phenotype in a mouse model of ALS, Experimental Neurology, vol.237, issue.1, pp.147-152, 2012.

A. Mantovani, A. Sica, S. Sozzani, P. Allavena, A. Vecchi et al., The chemokine system in diverse forms of macrophage activation and polarization, Trends in Immunology, vol.25, issue.12, pp.677-686, 2004.

O. Butovsky, S. Siddiqui, G. Gabriely, A. J. Lanser, B. Dake et al., Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS, Journal of Clinical Investigation, vol.122, issue.9, pp.3063-3087, 2012.

R. Shrivastava and N. Shukla, Attributes of alternatively activated (M2) macrophages, Life Sciences, vol.224, pp.222-231, 2019.

L. Martinez-merino, M. Iridoy, A. Galbete, M. Roldán, A. Rivero et al., Evaluation of Chitotriosidase and CC-Chemokine Ligand 18 as Biomarkers of Microglia Activation in Amyotrophic Lateral Sclerosis, Neurodegenerative Diseases, vol.18, issue.4, pp.208-215, 2018.

M. M. Tiemessen, A. L. Jagger, H. G. Evans, M. J. Van-herwijnen, S. John et al., CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages, Proceedings of the National Academy of Sciences, vol.104, issue.49, pp.19446-19451, 2007.

W. Holter, C. K. Goldman, L. Casabo, D. L. Nelson, W. C. Greene et al., Expression of functional IL 2 receptors by lipopolysaccharide and interferongamma stimulated human monocytes, J Immunol Baltim Md, vol.138, pp.2917-2939, 19501987.

F. Piehl, I. Kockum, M. Khademi, K. Blennow, J. Lycke et al., Plasma neurofilament light chain levels in patients with MS switching from injectable therapies to fingolimod, Multiple Sclerosis Journal, vol.24, issue.8, pp.1046-1054, 2017.

P. De-flon, K. Laurell, P. Sundström, K. Blennow, L. Söderström et al., Comparison of plasma and cerebrospinal fluid neurofilament light in a multiple sclerosis trial, Acta Neurologica Scandinavica, vol.139, issue.5, pp.462-468, 2019.

R. Ramchandani, D. A. Schoenfeld, and D. M. Finkelstein, Global rank tests for multiple, possibly censored, outcomes, Biometrics, vol.72, issue.3, pp.926-935, 2016.

R. K. Sheean, F. C. Mckay, E. Cretney, C. R. Bye, N. D. Perera et al., Association of Regulatory T-Cell Expansion With Progression of Amyotrophic Lateral Sclerosis, JAMA Neurology, vol.75, issue.6, p.681, 2018.