Age dependence of clinical and pathological manifestations of autoimmune demyelination - Implications for multiple sclerosis

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 ra rity 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) a utoimmune demyelination with many similarities to MS, has a uniform rapid o nset and a high incidence of clinical and pathological disease in adult (ma ture) animals. Like MS, EAE is most commonly seen and studied in female adu lts. In this study, age-related resistance to clinical EAE has been examine d 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 l ongest 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 EA E 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 develo ped onset of signs coincident with acute CNS lesions. This age-related resi stance 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 a nimals may be relevant to the increasing clinical expression of MS with mat uration, and may allow study of factors associated with the known occasiona l poor correlation of CNS inflammation and demyelination and clinical chang es in this disease.