title: Immune surveillance of the central nervous system in multiple sclerosis--relevance for therapy and experimental models.
abstract: Treatment of central nervous system (CNS) autoimmune disorders frequently involves the reduction, or depletion of immune-competent cells. Alternatively, immune cells are being sequestered away from the target organ by interfering with their movement from secondary lymphoid organs, or their migration into tissues. These therapeutic strategies have been successful in multiple sclerosis (MS), the most prevalent autoimmune inflammatory disorder of the CNS. However, many of the agents that are currently approved or in clinical development also have severe potential adverse effects that stem from the very mechanisms that mediate their beneficial effects by interfering with CNS immune surveillance. This review will outline the main cellular components of the innate and adaptive immune system that participate in host defense and maintain immune surveillance of the CNS. Their pathogenic role in MS and its animal model experimental autoimmune encephalomyelitis (EAE) is also discussed. Furthermore, an experimental model is introduced that may assist in evaluating the effect of therapeutic interventions on leukocyte homeostasis and function within the CNS. This model or similar models may become a useful tool in the repertoire of pre-clinical tests of pharmacological agents to better explore their potential for adverse events.
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, TX, USA.
authors.forename: Rehana Z
authors.initials: RZ
authors.lastname: Hussain
authors.affiliation: Teva Pharmaceuticals, Petah Tikva, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Hayardeny
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, TX, USA.
authors.forename: Petra C
authors.initials: PC
authors.lastname: Cravens
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center at Dallas, TX, USA.
authors.forename: Felix
authors.initials: F
authors.lastname: Yarovinsky
authors.affiliation: Histocompatibility and Transplant Immunology, Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, Houston, TX, USA.
authors.forename: Todd N
authors.initials: TN
authors.lastname: Eagar
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, TX, USA.
authors.forename: Benjamine
authors.initials: B
authors.lastname: Arellano
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, TX, USA.
authors.forename: Krystin
authors.initials: K
authors.lastname: Deason
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, TX, USA.
authors.forename: Cyd
authors.initials: C
authors.lastname: Castro-Rojas
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, TX, USA; Neurology Section, VA North Texas Health Care System, Medical Service, Dallas, TX, USA; Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Germany. Electronic address: olaf.stuve@utsouthwestern.edu.
authors.forename: Olaf
authors.initials: O
authors.lastname: Stüve
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental; D006801:Humans; D007157:Immunologic Surveillance; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology*
keywords: Autoimmunity; EAE; Experimental autoimmune encephalomyelitis; Immune surveillance; MS; Multiple sclerosis; Pharmacotherapy; Toxoplasmosis