Document 0562
 DOCN  M9650562
 TI    Adoptive transfer of experimental allergic encephalomyelitis after in
       vitro treatment with recombinant murine interleukin-12. Preferential
       expansion of interferon-gamma-producing cells and increased expression
       of macrophage-associated inducible nitric oxide synthase as
       immunomodulatory mechanisms.
 DT    9605
 AU    Waldburger KE; Hastings RC; Schaub RG; Goldman SJ; Leonard JP;
       Department of Preclinical Research, Genetics Institute, Andover,;
       Massachusetts 01810, USA.
 SO    Am J Pathol. 1996 Feb;148(2):375-82. Unique Identifier : AIDSLINE
       MED/96163272
 AB    In an adoptive transfer model of experimental allergic
       encephalomyelitis, stimulation of lymph node cells with proteolipid
       protein and recombinant murine interleukin (rmIL)-12 before cell
       transfer accelerated the onset and exacerbates clinical disease. In
       vitro stimulation with proteolipid protein in the presence of rmIL-12
       was associated with an increase in interferon-gamma-producing cells and
       a decrease in IL-4-producing cells, indicating a preferential expansion
       of Th1 effector cells. This was supported by the finding that severe
       disease with rapid onset could be transferred with as few as 10 x 10(6)
       rmIL-12-stimulated lymph node cells. Immunohistochemical analysis
       confirmed that the accelerated onset of disease after in vitro
       stimulation with rmIL-12 coincided with an acute inflammatory response
       in the central nervous system. At peak disease, both control and rmIL-12
       treatment groups exhibited extensive cellular infiltration with
       characteristic perivascular cuffing. No notable differences in either
       the cellular composition or cytokine expression within the lesions were
       seen between groups. However, the frequency of macrophages that stained
       positively for inducible nitric oxide synthase was increased in animals
       challenged with rmIL-12-treated lymph node cells. The results suggest
       that, in addition to promoting the preferential expansion of
       interferon-gamma-producing cells by rmIL-12 in vitro, secondary in vivo
       effects leading to macrophage activation and inducible nitric oxide
       synthase expression may contribute to the severe and protracted course
       of central nervous system inflammation in this model.
 DE    Animal  Brain Chemistry  Cells, Cultured  Encephalomyelitis,
       Allergic/*IMMUNOLOGY/METABOLISM  Freund's Adjuvant  Immunoenzyme
       Techniques  Immunotherapy, Adoptive  Interferon Type II/*BIOSYNTHESIS
       Interleukin-12/*PHARMACOLOGY  Interleukin-4/BIOSYNTHESIS  Lymphocyte
       Transformation  Macrophage Activation
       Macrophages/*ENZYMOLOGY/IMMUNOLOGY  Mice  Myelin Proteolipid
       Protein/IMMUNOLOGY  Nitric-Oxide Synthase/*BIOSYNTHESIS  Recombinant
       Proteins/PHARMACOLOGY  Th1 Cells/*IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).