Journal article
IL-12 is required for differentiation of pathogenic CD8+ T cell effectors that cause myocarditis
The Journal of clinical investigation, Vol.111(5), pp.671-680
03/01/2003
DOI: 10.1172/JCI200316867
PMCID: PMC151896
PMID: 12618521
Abstract
Cardiac antigen–specific CD8
+
T cells are involved in the autoimmune component of human myocarditis. Here, we studied the differentiation and migration of pathogenic CD8
+
T cell effector cells in a new mouse model of autoimmune myocarditis. A transgenic mouse line was derived that expresses cardiac myocyte restricted membrane-bound ovalbumin (CMy-mOva). The endogenous adaptive immune system of CMy-mOva mice displays tolerance to ovalbumin. Adoptive transfer of naive CD8
+
T cells from the ovalbumin-specific T cell receptor–transgenic (TCR-transgenic) OT-I strain induces myocarditis in CMy-mOva mice only after subsequent inoculation with ovalbumin-expressing vesicular stomatitis virus (VSV-Ova). OT-I effector T cells derived in vitro in the presence or absence of IL-12 were adoptively transferred into CMy-mOva mice, and the consequences were compared. Although IL-12 was not required for the generation of cytolytic and IFN-γ–producing effector T cells, only effectors primed in the presence of IL-12 infiltrated CMy-mOva hearts in significant numbers, causing lethal myocarditis. Furthermore, analysis of OT-I effectors collected from a mediastinal draining lymph node indicated that only effectors primed in vitro in the presence of IL-12 proliferated in vivo. These data demonstrate the importance of IL-12 in the differentiation of pathogenic CD8
+
T cells that can cause myocarditis.
Details
- Title: Subtitle
- IL-12 is required for differentiation of pathogenic CD8+ T cell effectors that cause myocarditis
- Creators
- Nir Grabie - Immunology Research Division andMichael W Delfs - Immunology Research Division andJason R Westrich - Immunology Research Division andVictoria A Love - Immunology Research Division andGeorge Stavrakis - Immunology Research Division andFerhaan Ahmad - Immunology Research Division andChristine E Seidman - Immunology Research Division andJonathan G Seidman - Immunology Research Division andAndrew H Lichtman - Immunology Research Division and
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.111(5), pp.671-680
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI200316867
- PMID
- 12618521
- PMCID
- PMC151896
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 03/01/2003
- Academic Unit
- Radiology; Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984025568702771
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