Frequency, heterogeneity and encephalitogenicity of T cells specific for myelin oligodendrocyte glycoprotein in naive outbred primates

Auto-reactive T cells present in healthy subjects remain in a state of unre sponsiveness, but may trigger autoimmunity under various situations. Althou gh myelin oligodendrocyte glycoprotein (MOG) is a potential target antigen in multiple sclerosis (MS), MOG-reactive T cell responses are present in th e blood of both healthy subjects and MS-affected individuals. To investigat e the disease-inducing potential and regulation of these autoreactive T cel ls in healthy outbred populations, we have characterized MOG-reactive T cel l clones obtained by limiting dilution from peripheral blood of unimmunized C. jacchus marmosets. We report an extraordinarily high prevalence of circ ulating MOG-reactive T cells in these naive animals (2.6 +/- 1.4/10(5) PBMC ), and a broadly diverse repertoire of epitope recognition encompassing at least three regions within the extracellular domain of MOG. Adoptive transf er of a MOG(21-40)-specific T cell clone resulted in mild clinical experime ntal allergic encephalomyelitis, characterized pathologically by rare foci of inflammation and minimal demyelination. We conclude that MOG-reactive T cells are present in healthy primates at a highly prevalent frequency, and are potentially capable of triggering central nervous system autoimmunity. Expansion of these autoreactive T cells must be tightly controlled to maint ain immune homeostasis in healthy individuals.