Age Dependence of Clinical and Pathological Manifestations of Autoimmune Demyelination : Implications for Multiple Sclerosis

• Published in: The American journal of pathology Vol. 155; no. 4; pp. 1147 - 1161
• Main Authors: Smith, Mary E, Eller, Nancy L, McFarland, Henry F, Racke, Michael K, Raine, Cedric S
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01.10.1999; American Society for Investigative Pathology
• Subjects: Age Factors; Animals; Antigen-Presenting Cells - immunology; Apoptosis; Biological and medical sciences; Cells, Cultured; Central Nervous System - immunology; Central Nervous System - pathology; Disease Models, Animal; Disease Progression; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Female; Flow Cytometry; Histocompatibility Antigens Class II - biosynthesis; In Situ Nick-End Labeling; Lymph Nodes - cytology; Lymph Nodes - immunology; Lymph Nodes - transplantation; Lymphocyte Activation - immunology; Male; Medical sciences; Mice; Multiple Sclerosis - immunology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Regular; Sex Factors; Time Factors; Autoimmunity; Immunopathology; Nervous system diseases; Multiple sclerosis; Encephalomyelitis; Rodentia; Inflammatory disease; Pathology; Vertebrata; Experimental disease; Mammalia; Mouse; Animal; Central nervous system disease; Dependence; Clinical investigation; Molecular biology; Age
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)65218-2

A prominent feature of the clinical spectrum of multiple sclerosis (MS) is its high incidence of onset in the third decade of life and the relative rarity of clinical manifestations during childhood and adolescence, features suggestive of age-related restriction of clinical expression. Experimental allergic encephalomyelitis (EAE), a model of central nervous system (CNS) autoimmune demyelination with many similarities to MS, has a uniform rapid onset and a high incidence of clinical and pathological disease in adult (mature) animals. Like MS, EAE is most commonly seen and studied in female adults. In this study, age-related resistance to clinical EAE has been examined with the adoptive transfer model of EAE in SJL mice that received myelin basic protein-sensitized cells from animals 10 days (sucklings) to 12 weeks (young adults) of age. A variable delay before expression of clinical EAE was observed between the different age groups. The preclinical period was longest in the younger (<14 days of age) animals, and shortest in animals 6 to 8 weeks old at time of transfer. Young animals initially resistant to EAE eventually expressed well-developed clinical signs by 6 to 7 weeks of age. This was followed by a remitting, relapsing clinical course. For each age at time of sensitization, increased susceptibility of females compared to males was observed. Examination of the CNS of younger animal groups during the preclinical period showed lesions of acute EAE. Older age groups developed onset of signs coincident with acute CNS lesions. This age-related resistance to clinical EAE in developing mice is reminiscent of an age-related characteristic of MS previously difficult to study in vivo. The associated subclinical CNS pathology and age-related immune functions found in young animals may be relevant to the increasing clinical expression of MS with maturation, and may allow study of factors associated with the known occasional poor correlation of CNS inflammation and demyelination and clinical changes in this disease.