Regulation of the effector stages of experimental autoimmune encephalomyelitis via neuroantigen-specific tolerance induction. III. A role for anergy/deletion

Lit Jen Tan, Carol L. Vanderlugt, Bradford L. McRae, Stephen D. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Our previous work has shown that specific peripheral immune tolerance induced by the intravenous administration of ECDI-fixed, antigen-coupled syngeneic splenocytes is an extremely efficient method for prevention and treatment of chronic relapsing experimental autoimmune encephalomyelitis (R-EAE) in susceptible SJL/J mice. The current study examined the mechanisms by which unresponsiveness is induced in primed encephalitogenic T cells. The results indicate that the inhibition of MBP-specific T cells by the i.v. injection of MBP-coupled splenocytes is not due to the induction of antigen-specific regulatory T cells, but rather to the induction of anergy/deletion of the effector cells. This conclusion is supported by the findings that spleen or lymph node cells isolated from MBP-tolerant mice fail to inhibit the adoptive transfer of R-EAE in cotransfer assays, and that tolerance is not inhibited by prior thymectomy or prior treatment with cyclophosphamide or anti-CD8 monoclonal antibody. In contrast, we demonstrate that splenocytes from MBP-tolerized, asymptomatic mice have a significantly reduced ability to serially transfer R-EAE to naive secondary recipients following antigen re-activation in vitro, in the first several weeks following tolerization, but that the ability to serially transfer R-EAE returns to sham tolerant control levels within 1-2 months. We also demonstrate a significantly reduced precursor frequency of MBP-specific, IL-2-producing T cells in the MBP-tolerant within three days of treatment. Collectively, the data most closely support a model wherein inhibition of MBP-specific encephalitogenic CD4+ effector T cells by i.v. injected MBP-coupled splenocytes is due to the direct induction of anergy/deletion from which they can recover over time.

Original languageEnglish (US)
Pages (from-to)13-28
Number of pages16
JournalAutoimmunity
Volume27
Issue number1
DOIs
StatePublished - 1998

Keywords

  • Anergy
  • Central nervous system
  • Experimental autoimmune encephalomyelitis (EAE)
  • Multiple sclerosis
  • Myelin basic protein (MBP)
  • Tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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