Tolerogenic forms of auto-antigens and cytokines in the induction of resistance to experimental allergic encephalomyelitis

L. Santambrogio, G. M. Crisi, J. Leu, G. M. Hochwald, T. Ryan, G. J. Thorbecke

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Abstract

Resistance to experimental allergic encephalomyelitis (EAE) induction by homogenized myelin (MSCH) in complete Freund's adjuvant (CFA) and pertussigen (P) in SJL mice was seen 1 week after intravenous injection of PLP 139-151 coupled to spleen cells (PLP-ECDI-SP). Although this resistance could be transferred by spleen cells enriched for CD8+ T cells and thus had a component of immunoregulatory T cells, it was primarily due to anergy, as it was reversible by four daily injections of interleukin (II)-2 starting 3 days after the PLP-ECDI-SP. Earlier treatment with IL-2 did not reverse the tolerance. In view of the known higher sensitivity to anergy induction of Th1 than of Th2 cells, a change in the cytokine balance in the response to MSCH + CFA after anergy induction might be responsible for the resistance to EAE induction. The effect of treatment with cytokines alone on induction of EAE was therefore also determined. Short-term (1-2 weeks) daily pretreatment with IL-2 (4000 U) or TGF-β2 (1 μ g) somewhat decreased the susceptibility to subsequent EAE induction, but IL-4 (5 ng), IL-10 (5 μ g) or IL-12 (50-200 ng) had no effect under those conditions, even if low doses of PLP were injected simultaneously. Daily injections of IL-4 over an 8-week period prior to immunization, however, significantly lowered the incidence of EAE. Simultaneous injections of IFN-γ (2000 U/day) completely abolished this effect of IL-4. The effect of these cytokines administered immediately after the immunization with MSCH + CFA + P was also examined. As shown earlier, TGF-β2 (100-1000 ng/day) caused a marked protection when it was given intraperitoneally on days 5-9 after injection of MSCH + CFA. IL-4 (5 ng/day), in contrast, was very protective when administered on days 0-4 and less so when given on days 5-9 or even on days 0-12. IL-10 (1 μg/day) was not protective under these conditions and IL-12 (50 ng/day) significantly increased the severity and mortality of EAE when given on days 0-4 after MSCH + CFA.

Original languageEnglish (US)
Pages (from-to)211-222
Number of pages12
JournalJournal of Neuroimmunology
Volume58
Issue number2
DOIs
Publication statusPublished - May 1995

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Keywords

  • Anergy
  • Experimental allergic encephalomyelitis
  • Interleukin-10
  • Interleukin-12
  • Interleukin-2
  • Interleukin-4
  • Proteolipid protein-coupled spleen cells
  • Tolerance
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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