PMID- 8642780
OWN - NLM
STAT- MEDLINE
DCOM- 19960716
LR  - 20091119
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 74
IP  - 5
DP  - 1996 May
TI  - Cardiac myosin-induced myocarditis: target recognition by autoreactive T cells 
      requires prior activation of cardiac interstitial cells.
PG  - 845-52
AB  - Immunization with cardiac myosin causes T cell-mediated myocarditis in 
      genetically predisposed mice and serves as a model for autoimmune heart disease. 
      The normal heart is not susceptible to T cells autoreactive with cardiac myosin; 
      therefore, we investigated the conditions that are required to facilitate 
      recognition of the target tissue. A.SW mice were immunized with cardiac myosin on 
      Days 0 and 7. Major histocompatibility antigen (MHC Ag) and intercellular 
      adhesion molecule-1 (ICAM-1) expression in the heart tissue was investigated by 
      immunohistochemical techniques shortly before disease onset (ie, on Day 9). At 
      this time point, cardiac interstitial cells expressing class II but not class I 
      MHC Ag were significantly increased. In addition, endothelial ICAM-1 expression 
      was strongly up-regulated. Myofibers did not show expression of these markers, 
      and T cells were virtually absent. Because lipopolysaccaride (LPS) induced a 
      similar distribution of class II MHC Ag and ICAM-1 in the myocardial tissue and 
      because these molecules could be crucial to disease onset, we determined whether 
      treatment with this immunomodulator renders the heart susceptible to passively 
      transferred myosin-reactive T cells. We found that concanavalin A-activated 
      spleen cells from myosin-immunized donors induced myocarditis in LPS-primed 
      recipients, whereas normal mice were resistant to the injection of such cells. 
      Increased class II MHC Ag expression after LPS-treatment was mediated by TNF 
      because LPS-primed mice genetically lacking the TNF receptor failed to increase 
      class II MHC Ag expression in the heart tissue. In summary, these results suggest 
      that in cardiac myosin-induced myocarditis, expression of interstitial class II 
      MHC Ag and/or endothelial ICAM-1 is a prerequisite for target organ recognition 
      by autoreactive T cells.
FAU - Pummerer, C L
AU  - Pummerer CL
AD  - Department of Pediatrics, University of Innsbruck Medical School, Austria.
FAU - Grassl, G
AU  - Grassl G
FAU - Sailer, M
AU  - Sailer M
FAU - Bachmaier, K W
AU  - Bachmaier KW
FAU - Penninger, J M
AU  - Penninger JM
FAU - Neu, N
AU  - Neu N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Antigens, CD)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 3.6.4.1 (Myosins)
SB  - IM
MH  - Animals
MH  - Antigens, CD/analysis/genetics/physiology
MH  - Autoimmune Diseases/*immunology
MH  - Histocompatibility Antigens Class I/analysis
MH  - Histocompatibility Antigens Class II/analysis
MH  - Immunization
MH  - Immunoenzyme Techniques
MH  - Immunotherapy, Adoptive
MH  - Intercellular Adhesion Molecule-1/analysis
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Myocarditis/*immunology
MH  - Myocardium/*immunology/pathology
MH  - Myosins/*immunology
MH  - Receptors, Tumor Necrosis Factor/genetics/physiology
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - T-Lymphocytes/*immunology
MH  - Tumor Necrosis Factor-alpha/physiology
EDAT- 1996/05/01 00:00
MHDA- 1996/05/01 00:01
CRDT- 1996/05/01 00:00
PHST- 1996/05/01 00:00 [pubmed]
PHST- 1996/05/01 00:01 [medline]
PHST- 1996/05/01 00:00 [entrez]
PST - ppublish
SO  - Lab Invest. 1996 May;74(5):845-52.