doi: 10.1161/CIRCRESAHA.107.158238
© 2007 American Heart Association, Inc.
Editorials |
Crosstalk Between Cytotoxic T-Lymphocyte–Associated Antigen-4 and Interleukin-12 in Cytotoxic T-Lymphocyte–Mediated Myocarditis
Adding Another Link to the Chain
From the Nephrology (S.S.A., C.A.E.) and Cardiology (M.L.L.) Divisions, Department of Medicine, University of Texas Health Science Center, San Antonio.
Correspondence to Merry L. Lindsey, PhD, Assistant Professor, Medicine/Cardiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900. E-mail lindseym@uthscsa.edu
See related article, pages 248–257
Key Words: myocarditis • lymphocyte • CTLA-4 • mice
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Myocarditis, or inflammation of the myocardium, may arise from immune-mediated destruction of myocardium harboring foreign viral or microbial antigens or from a dysregulated immune system that is unable to distinguish self myocardial antigens from foreign antigens. Of these causes, immune-mediated myocarditis is a primary etiology. Although myocarditis remains a relatively rare event, prognosis following diagnosis remains poor, and 6 year mortality rates approaching 30% have been reported.1 T lymphocytes mediate acquired immunity against a foreign antigen via humoral or cell-mediated mechanisms and hence may affect the outcome of myocarditis. T-lymphocyte involvement was first shown in the 1970s, when T-lymphocyte depletion decreased the inflammatory response and increased survival in a murine model of Coxsackie virus B3–induced myocarditis.2 Since then, research has focused on delineating the roles of individual lymphocyte subtypes. In this issue, Love et al examine the role of cytotoxic T-lymphocyte–associated antigen (CTLA)-4 in CD8+ T-cell regulation by using a transgenic model of CD8+ T-lymphocyte–mediated myocarditis.3
One subset of T lymphocytes is the CD8+ T lymphocytes, which are antigen-specific cytotoxic cells that normally protect against infection by killing infected cells via effector molecules such as perforins and granzymes. In the myocardium, CD8+ lymphocytes regulate both myocarditis and allograft rejection by differentiating into cytotoxic T lymphocytes (CTLs).4,5 Differentiation involves several effector functions, including increased proliferation and cytokine production.6
The CTL response to an infection can be divided into 4 phases. The first is the activation phase, in which naive CTL precursors are primed, undergo cell expansion, acquire effector function, travel to
Related Article:
Circ. Res. 2007 101: 248-257.