Oral tolerization with cardiac myosin peptide (614-629) ameliorates experimental autoimmune myocarditis: role of STAT 6 genes in BALB/CJ mice.
BACKGROUND
Experimental autoimmune myocarditis (EAM) is mediated by myocardial infiltration by myosin-specific T cells secreting inflammatory cytokines.


METHODS
To clarify the role of cytokines in EAM, we compared STAT 6-deficient ((-/-)) with STAT 4(-/-) and wild-type (BALB/CJ) mice following immunization with cardiac myosin peptide (614-629).


RESULTS
Wild-type mice developed severe disease with a small increase in severity in STAT 6(-/-) mice, while STAT 4(-/-) mice were resistant to EAM. STAT 6(-/-) mice had increased splenocyte proliferation and INF-gamma production versus wild type, while STAT 4(-/-) mice had decreased proliferation and INF-gamma. Following oral administration of myosin (614-629), tolerization was induced in wild-type mice evidenced by amelioration of myocarditis and up-regulation of IL-4. Adoptive transfer of splenocytes from orally tolerized mice resulted in inhibition of disease in STAT 6(-/-) mice.


CONCLUSIONS
These results demonstrate that oral tolerization ameliorates EAM in BALB/CJ mice and indicate a down-regulatory role for STAT 6 genes.
Children's Hospital and Harvard Medical School, Boston, MA 02115, USA. pgonnell@bidmc.harvard.edu
Patricia A
PA
Gonnella
Pedro J
PJ
Del Nido
Francis X
FX
McGowan
D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D024722:Cardiac Myosins / Q000008:administration & dosage / Q000276:immunology*; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000378:metabolism
D010455:Peptides; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; C494091:Stat4 protein, mouse; C494100:Stat6 protein, mouse; D015847:Interleukin-4; D007371:Interferon-gamma; D024722:Cardiac Myosins