Regulation of autoreactive T cell function by oral tolerance to self-antigens

Ann N Y Acad Sci. 2004 Dec;1029:172-9. doi: 10.1196/annals.1309.033.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Administration, Oral
  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigens / immunology
  • Autoantigens / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Humans
  • Immunity, Mucosal*
  • Models, Immunological
  • T-Lymphocytes / immunology*

Substances

  • Antigens
  • Autoantigens