Reduced myocarditis following Coxsackievirus infection in cellular FLICE inhibitory protein – long form‐transgenic mice
Open Access
- 9 October 2006
- journal article
- Published by Wiley in Immunology
- Vol. 119 (4), 541-550
- https://doi.org/10.1111/j.1365-2567.2006.02469.x
Abstract
Cellular FLICE inhibitory protein – long form (c-FLIPL) is a caspase-defective homologue of caspase-8 that blocks apoptosis by death receptors. c-FLIPL expression in T cells can also augment activation of the mitogen-activated protein kinase, extracellular signal-related kinase, as well as nuclear factor-κB. This contributes to increased production of interleukin-2 and CD25, resulting in hyperproliferation of T cells from c-FLIPL-transgenic mice. c-FLIP also heterodimerizes with and activates caspase-8, resulting in increased death of T cells and a selection of a T helper 2 cytokine profile. The effects of c-FLIP on cytolytic function of CD8+ T cells have not been examined previously. We studied the cytolytic capacity of T cells from c-FLIPL-transgenic mice using an antigen-specific system, as well as the consequences during a viral immune response to Coxsackievirus B3 (CVB3). The increased T-cell receptor (TCR) signalling due to c-FLIP did not alter the cytolytic machinery but did reduce cytotoxicity because of decreased surface expression of TCR and CD8. It also produced a Tc2 cytokine profile. These effects of c-FLIP collectively served to diminish the severity of CVB3-induced myocarditis.Keywords
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