Regulation of autoreactive T cell function by oral tolerance to self-antigens.
The oral administration of neuroantigens can suppress as well as treat autoimmune disease. Using EAE as a model system, we examined the antigen-presenting cell in oral tolerance. Expansion of dendritic cells (DCs) prior to or after disease is established facilitated oral tolerance. Transfer of oral antigen-loaded DCs resulted in protection from EAE by induction of IL-4 and IL-5 in recipient animals. LPS treatment of donors abrogated the ability of DCs to transfer protection from EAE, emphasizing the importance of the DC activation state. T cells exposed to orally administered antigen were monitored in TCR transgenic mice and found to undergo activation followed by deletion. The thymus plays a critical role in oral tolerance since thymectomized mice could not be tolerized. The thymus is postulated to be a site for deletion of autoreactive T cells or a site for generation of regulatory T cells.
Whitacre
Caroline C
CC
Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University College of Medicine and Public Health, Columbus, Ohio 43210, USA. whitacre.3@osu.edu
Song
Fei
F
Wardrop
Richard M
RM
Campbell
Kim
K
McClain
Melanie
M
Benson
Jacqueline
J
Guan
Zhen
Z
Gienapp
Ingrid
I
D000284:Administration, Oral; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D001324:Autoantigens