title: Multiple sclerosis: a disorder of altered T-cell homeostasis.
abstract: Uncertainty exists as to whether similar or different mechanisms contribute to the pathogenesis of different subtypes of multiple sclerosis (MS). Detailed analysis of naive T cell homeostasis shows that patients with relapsing-remitting MS (RRMS) and with primary progressive MS (PPMS) have early-onset thymic involution that causes reduced thymic output. The reduced thymic output leads to secondary peripheral homeostatic alterations in naïve CD4 T-cells, which closely mimic T-cell alterations observed in an experimental animal model of diabetes mellitus. Homeostatic T-cell receptor (TCR) signalling and proliferation of naïve T cells are induced by self-peptides. Consequently, the findings of increased TCR signalling of naïve CD4 T-cells, without increased proliferation, in PPMS, and the increased homeostatic proliferation of naïve CD4 T-cells in RRMS favour the development of autoimmunity. Thus, it seems highly likely that peripheral T-cell alterations secondary to a thymic abnormality contribute to the pathogenesis of both MS subtypes.
authors.affiliation: Department of Pathology, McGill University, Duff Medical Building, 3775 rue University, Montreal, QC, Canada H3A 2B4.
authors.forename: David G
authors.initials: DG
authors.lastname: Haegert
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