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 of unimmunized C. jacchus marmosets. We report an extraordinarily high prevalence of circulating 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 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.
Villoslada
P
P
Department of Neurology, University of California, San Francisco, USA. pvilloslada@unav.es
Abel
K
K
Heald
N
N
Goertsches
R
R
Hauser
S L
SL
Genain
C P
CP
D000818:Animals; D002144:Callithrix; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology*; D000939:Epitopes; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D000939:Epitopes; C571328:Mog protein, rat; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein