| First Author | Taqueti VR | Year | 2006 |
| Journal | J Immunol | Volume | 177 |
| Issue | 9 | Pages | 5890-901 |
| PubMed ID | 17056513 | Mgi Jnum | J:140534 |
| Mgi Id | MGI:3814035 | Doi | 10.4049/jimmunol.177.9.5890 |
| Citation | Taqueti VR, et al. (2006) T-bet controls pathogenicity of CTLs in the heart by separable effects on migration and effector activity. J Immunol 177(9):5890-901 |
| abstractText | CD8+ CTL contribute to the pathogenesis of myocarditis and cardiac allograft rejection. Using a transgenic model of myocarditis, we examined the role of the transcription factor T-bet in the differentiation of pathogenic cardiac Ag-specific CTL. We demonstrate that T-bet-deficient CTL are significantly impaired in their ability to cause disease, despite intact proliferation and activation phenotypes. In the absence of T-bet, there is markedly reduced expression of the chemokine receptor CXCR3, and CXCR3-gene knockout CTL are significantly less pathogenic than control CTL. Retroviral-mediated CXCR3 expression in T-bet-deficient CD8+ T cells reconstitutes their ability to infiltrate but not to damage the heart, establishing that CD8+ T cell pathogenicity is related to T-bet-dependent CXCR3 expression, reduced cytotoxicity, and enhanced regulation. These findings highlight the potential therapeutic benefit of targeting T-bet-regulated gene expression and CXCR3-dependent migration in immune-mediated heart disease. |
