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Reduced myocarditis following Coxsackievirus infection in cellular FLICE inhibitory protein – long form‐transgenic mice
Author(s) -
Huber Sally,
Dohrman Austin,
Sartini Danielle,
Budd Ralph C.
Publication year - 2006
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2006.02469.x
Subject(s) - biology , il 2 receptor , cd8 , cytolysis , flip , cytokine , caspase 8 , immune system , necroptosis , microbiology and biotechnology , cytotoxic t cell , t cell , apoptosis , viral myocarditis , immunology , programmed cell death , caspase , virus , in vitro , biochemistry
Summary Cellular FLICE inhibitory protein – long form (c‐FLIP L ) is a caspase‐defective homologue of caspase‐8 that blocks apoptosis by death receptors. c‐FLIP L 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‐FLIP L ‐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‐FLIP L ‐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.