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 unresponsiveness, but may trigger autoimmunity under various situations. Although myelin oligodendrocyte glycoprotein (MOG) is a potential target antigen in multiple sclerosis (MS), MOG‐reactive T cell responses are present in the blood of both healthy subjects and MS‐affected individuals. To investigate the disease‐inducing potential and regulation of these autoreactive T cells in healthy outbred populations, we have characterized MOG‐reactive T cell clones obtained by limiting dilution from peripheral blood ofunimmunized C. jacchus marmosets. We report an extraordinarily high prevalence of circulating MOG‐reactive T cells in these naive animals (2.6 ± 1.4 / 105 PBMC), and a broadly diverse repertoire of epitope recognition encompassing at least three regions within the extracellular domain of MOG. Adoptive transfer of a MOG21 – 40‐specific T cell clone resulted in mild clinical experimental 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 maintain immune homeostasis in healthy individuals.