Tolerogenic forms of auto-antigens and cytokines in the induction of resistance to experimental allergic encephalomyelitis. Academic Article uri icon

Overview

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-beta 2 (1 micrograms) somewhat decreased the susceptibility to subsequent EAE induction, but IL-4 (5 ng), IL-10 (5 micrograms) 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-gamma (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-beta 2 (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 microgram/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.

publication date

  • May 1, 1995

Research

keywords

  • Autoantigens
  • Encephalomyelitis, Autoimmune, Experimental
  • Immune Tolerance
  • Interleukin-2
  • Myelin Proteolipid Protein

Identity

Scopus Document Identifier

  • 0029025863

PubMed ID

  • 7759610

Additional Document Info

volume

  • 58

issue

  • 2