Abstract | INTRODUCTION: Experimental autoimmune myocarditis (EAM) is mediated by myocardial infiltration by myosin-specific T cells secreting inflammatory cytokines. MATERIALS AND 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. CONCLUSION: These results demonstrate that oral tolerization ameliorates EAM in BALB/CJ mice and indicate a down-regulatory role for STAT 6 genes.
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Authors | Patricia A Gonnella, Pedro J Del Nido, Francis X McGowan |
Journal | Journal of clinical immunology
(J Clin Immunol)
Vol. 29
Issue 4
Pg. 434-43
(Jul 2009)
ISSN: 1573-2592 [Electronic] Netherlands |
PMID | 19353248
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Peptides
- STAT4 Transcription Factor
- STAT6 Transcription Factor
- Stat4 protein, mouse
- Stat6 protein, mouse
- Interleukin-4
- Interferon-gamma
- Cardiac Myosins
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Topics |
- Administration, Oral
- Adoptive Transfer
- Animals
- Autoimmune Diseases
(immunology, pathology)
- Cardiac Myosins
(administration & dosage, immunology)
- Immune Tolerance
- Interferon-gamma
(biosynthesis, immunology)
- Interleukin-4
(biosynthesis, immunology)
- Mice
- Mice, Inbred BALB C
- Mice, Knockout
- Myocarditis
(immunology, pathology)
- Peptides
(administration & dosage, immunology)
- STAT4 Transcription Factor
(genetics, immunology, metabolism)
- STAT6 Transcription Factor
(genetics, immunology, metabolism)
- Spleen
(immunology, metabolism)
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