The innate immune response to adjuvants dictates the adaptive immune response to autoantigens

Maria A Staykova, David Liñares, Susan A Fordham, Judith T Paridaen, David O Willenborg

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To elucidate the role of innate immunity in susceptibility to the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we induced EAE by immunization with spinal cord homogenate (SCH) plus complete Freund adjuvant or carbonyl iron in 3 inbred rat strains. Lewis are considered "susceptible," PVG/c-Rt7a (PVG) as "semisusceptible," and Brown Norway (BN) as "resistant" to EAE. Immunization with SCH-carbonyl iron resulted in clinical disease in all 3 strains, but the pathologic features of EAE in the resistant BN and the semisusceptible PVG rats differed from those in the Lewis and PVG model of EAE induced with SCH-complete Freund adjuvant. In BN and PVG rats, there were numerous inflammatory lesions with prominent involvement of microglia and, to a lesser extent, perivascular macrophages. These data suggest that different levels of activation of the innate immune system by different adjuvants determine whether EAE will or will not develop. Accordingly, the widely accepted scale of susceptibility to EAE development (Lewis > PVG > BN) should be revised because it does not take into account the important contribution of the composition of the adjuvant to the quality and quantity of the innate immune response and, consequently, to the generation and extent of the pathogenic T-cell-mediated, that is, adaptive, autoimmune disease.

Original languageEnglish
Pages (from-to)543-554
Number of pages12
JournalJournal of neuropathology and experimental neurology
Issue number6
Publication statusPublished - Jun-2008
Externally publishedYes


  • Adjuvants, Immunologic
  • Animals
  • Autoantigens
  • Encephalomyelitis, Autoimmune, Experimental
  • Flow Cytometry
  • Freund's Adjuvant
  • Genetic Predisposition to Disease
  • Immunity, Innate
  • Immunohistochemistry
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interferon-gamma
  • Iron Compounds
  • Macrophage Activation
  • Nitric Oxide
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spinal Cord
  • T-Lymphocytes
  • Journal Article
  • Research Support, Non-U.S. Gov't

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