PMID- 9024154
OWN - NLM
STAT- MEDLINE
DCOM- 19970311
LR  - 20190623
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 95
IP  - 3
DP  - 1997 Feb 4
TI  - Low-molecular-weight tumor necrosis factor receptor p55 controls induction of 
      autoimmune heart disease.
PG  - 655-61
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is involved in the 
      pathogenesis of myocarditis and can bind to either tumor necrosis factor receptor 
      (TNF-R) p55 or TNF-Rp75. However, it is not known which TNF-R mediates the 
      specific functions of TNF in disease. To determine the role of the TNF/TNF-R 
      system in chronic heart disease, we used a murine model of cardiac myosin-induced 
      myocarditis that closely resembles the chronic stages of virus-induced 
      myocarditis in humans. METHODS AND RESULTS: Mice lacking TNF-Rp55 expression 
      after targeted disruption of the TNF-Rp55 gene were backcrossed into a genetic 
      background susceptible to the induction of myocarditis with cardiac myosin. Here, 
      we demonstrate that TNF-Rp55 gene-deficient mice did not develop any inflammatory 
      infiltration into the heart after autoantigen injection, whereas control 
      littermates showed autoimmune myocarditis at high prevalence and severity. 
      Despite the absence of autoimmune heart disease, TNF-Rp55-/- mice produced 
      cardiac myosin-specific IgG autoantibodies, indicating that activation of 
      autoaggressive T and B lymphocytes had occurred. However, heart interstitial 
      cells failed to express major histocompatibility complex (MHC) class II molecules 
      in TNF-Rp55-/- animals, and adoptive transfer of autoreactive T cells resulted in 
      heart disease only in TNF-Rp55-/- but not in TNF-Rp55-/- littermates. 
      CONCLUSIONS: Cardiac myosin-induced myocarditis is dependent on autoaggressive T 
      cells and on autoantigen presentation in association with MHC class II molecules 
      within the heart. Thus, lack of TNF-Rp55 expression could interfere with either 
      lymphocyte activation or target organ susceptibility. The data presented here 
      show that the TNF-Rp55 is a key regulator for the induction of autoimmune heart 
      disease by its controlling target organ susceptibility.
FAU - Bachmaier, K
AU  - Bachmaier K
AD  - Amgen Institute, Ontario Cancer Institute, Canada.
FAU - Pummerer, C
AU  - Pummerer C
FAU - Kozieradzki, I
AU  - Kozieradzki I
FAU - Pfeffer, K
AU  - Pfeffer K
FAU - Mak, T W
AU  - Mak TW
FAU - Neu, N
AU  - Neu N
FAU - Penninger, J M
AU  - Penninger JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Autoantibodies)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - EC 3.6.4.1 (Myosins)
SB  - IM
CIN - Circulation. 1997 Feb 4;95(3):551-2. PMID: 9024133
MH  - Animals
MH  - Autoantibodies/immunology
MH  - Autoimmune Diseases/*etiology/immunology/pathology
MH  - Disease Susceptibility/immunology
MH  - Dogs
MH  - Histocompatibility Antigens Class II/immunology
MH  - Mice
MH  - Mice, Knockout/genetics
MH  - Molecular Weight
MH  - Myocarditis/*etiology/immunology/pathology
MH  - Myocardium/immunology/pathology
MH  - Myosins/immunology
MH  - Receptors, Tumor Necrosis Factor/chemistry/genetics/*physiology
MH  - T-Lymphocytes/immunology/transplantation
EDAT- 1997/02/04 00:00
MHDA- 1997/02/04 00:01
CRDT- 1997/02/04 00:00
PHST- 1997/02/04 00:00 [pubmed]
PHST- 1997/02/04 00:01 [medline]
PHST- 1997/02/04 00:00 [entrez]
AID - 10.1161/01.cir.95.3.655 [doi]
PST - ppublish
SO  - Circulation. 1997 Feb 4;95(3):655-61. doi: 10.1161/01.cir.95.3.655.