       Document 0914
 DOCN  M95A0914
 TI    The time course and characterization of mercuric chloride-induced
       immunopathology in the brown Norway rat.
 DT    9510
 AU    Qasim FJ; Thiru S; Mathieson PW; Oliveira DB; Department of Medicine,
       Cambridge University School of Clinical; Medicine, Addenbrooke's
       Hospital, UK.
 SO    J Autoimmun. 1995 Apr;8(2):193-208. Unique Identifier : AIDSLINE
       MED/95336595
 AB    Mercuric chloride (HgCl2) induces an autoimmune syndrome in the Brown
       Norway (BN) rat which includes widespread tissue injury. There is
       necrotizing leucocytoclastic vasculitis in the gut with maximal injury
       occurring 2 weeks after the start of HgCl2 injections. There is evidence
       that disease is driven by Th2-like cell (CD4+CD45RClow) activity and
       that Th1-like cells (CD4+CD45RChigh) may be protective. Using the
       established protocol of five injections of HgCl2 over 10 days, we have
       studied in greater detail the presence and extent of vasculitis and
       changes in T cell subsets from 12 h to 20 days after the first
       injection. Animals were killed at various time points and necropsies
       performed. Tissue injury was scored both macroscopically and
       histologically, with immunohistochemistry for T cell subsets. Flow
       cytometry was used to determine T cell subsets in peripheral blood,
       mesenteric lymph node (LN) and spleen. Tissue injury was seen as early
       as 24 h after the first injection of HgCl2. The size of lesions and
       extent of vasculitis increased over the next two weeks with partial
       resolution at day 20. We confirmed that of peripheral blood T cells in
       the BN rat, less than 20% were CD8+ and a similar proportion were
       CD4+CD45RChigh, but found that less than 75% of CD8+ T cells were
       CD45RChigh (in other strains of rat more than 90% CD8+ T cells are
       CD45RChigh). Within 48 h, HgCl2 caused a rise in the proportion of CD4+
       T cells in spleen, LN and peripheral blood which then fell towards
       normal at peak tissue injury. The proportion of CD4+CD45RClow T cells
       rose in the first week, but subsequently fell, with reciprocal changes
       in CD4+CD45RChigh T cells. There was an increase in CD8+ T cells towards
       peak disease. The speed of onset of tissue injury suggests that cells
       other than T cells may be involved in the primary induction of
       vasculitis, although Th2-like cells may be important in further tissue
       injury and in B cell activation. The rise in CD8+ and Th1-like cells
       towards peak disease supports the hypothesis that they are involved in
       disease regulation.
 DE    Animal  Antibody Specificity  Autoantibodies/BIOSYNTHESIS/IMMUNOLOGY
       Autoimmune Diseases/*CHEMICALLY INDUCED/GENETICS/IMMUNOLOGY/  PATHOLOGY
       Cecum/PATHOLOGY  Disease Progression  Female  Intestinal
       Mucosa/PATHOLOGY  Lung/PATHOLOGY  Lymph Nodes/PATHOLOGY  Lymphocyte
       Count  Lymphoproliferative Disorders/*CHEMICALLY INDUCED/GENETICS/
       IMMUNOLOGY/PATHOLOGY  Male  Mercuric Chloride/*TOXICITY
       Neutrophils/IMMUNOLOGY/PATHOLOGY  Peroxidase/IMMUNOLOGY  Rats  Rats,
       Inbred BN/*IMMUNOLOGY  Skin/PATHOLOGY  Spleen/PATHOLOGY  Support,
       Non-U.S. Gov't  T-Lymphocyte Subsets/*IMMUNOLOGY  Th1 Cells/IMMUNOLOGY
       Th2 Cells/IMMUNOLOGY  Time Factors  Vasculitis,
       Hypersensitivity/*CHEMICALLY INDUCED/GENETICS/  IMMUNOLOGY/PATHOLOGY
       JOURNAL ARTICLE

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

