HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Revisiting tolerance induced by autoantigen in incomplete Freund's adjuvant.

Abstract
Injection of autoantigens in IFA has been one of the most effective ways of preventing experimental, T cell-mediated, autoimmune disease in mice. The mechanism that underlies this protection has, however, remained controversial, with clonal deletion, induction of suppressor cells or of type 2 immunity being implicated at one time or another. Using high resolution enzyme-linked immunospot (ELISPOT) analysis, we have revisited this paradigm. As models of autoimmunity against sequestered and readily accessible autoantigens, we studied experimental allergic encephalomyelitis, induced by myelin oligodendrocyte glycoprotein, proteolipid protein, myelin basic protein, and renal tubular Ag-induced interstitial nephritis. We showed that the injection of each of these Ags in IFA was immunogenic and CD4 memory cells producing IL-2, IL-4, and IL-5, but essentially no IFN-gamma. IgG1, but not IgG2a, autoantibodies were produced. The engaged T cells were not classic Th2 cells in that IL-4 and IL-5 were produced by different cells. The IFA-induced violation of self tolerance, including the deposition of specific autoantibodies in the respective target organs, occurred in the absence of detectable pathology. Exhaustion of the pool of naive precursor cells was shown to be one mechanism of the IFA-induced tolerance. In addition, while the IFA-primed T cells acted as suppressor cells, in that they adoptively transferred disease protection, they did not interfere with the emergence of a type 1 T cell response in the adoptive host. Both active and passive tolerance mechanisms, therefore, contribute to autoantigen:IFA-induced protection from autoimmune disease.
AuthorsP S Heeger, T Forsthuber, C Shive, E Biekert, C Genain, H H Hofstetter, A Karulin, P V Lehmann
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 164 Issue 11 Pg. 5771-81 (Jun 01 2000) ISSN: 0022-1767 [Print] United States
PMID10820255 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Autoantibodies
  • Autoantigens
  • Cytokines
  • Immunoglobulin G
  • Lipids
  • incomplete Freund's adjuvant
  • Freund's Adjuvant
Topics
  • Adoptive Transfer
  • Animals
  • Autoantibodies (biosynthesis, metabolism)
  • Autoantigens (administration & dosage, immunology)
  • Autoimmune Diseases (immunology, pathology, prevention & control)
  • Cytokines (biosynthesis)
  • Female
  • Freund's Adjuvant (administration & dosage, immunology)
  • Immune Tolerance (immunology)
  • Immunoglobulin G (biosynthesis)
  • Injections, Intraperitoneal
  • Lipids
  • Lymphocyte Transfusion
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Organ Specificity (immunology)
  • Spleen (cytology, transplantation)
  • Stem Cells (immunology, metabolism)
  • Th1 Cells (immunology, metabolism)
  • Th2 Cells (immunology, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: