Exacerbated inflammatory responses in transgenic mice expressing an inhibitor of apoptosis protein (OpIAP)

Abstract

Members of the inhibitor of apoptosis protein family are involved not only in suppressing apoptosis, but also in signal transduction, cell division, and are associated with some types of cancers. Here we show that transgenic expression of the inhibitor of apoptosis protein OpIAP in murine T lymphocytes leads to a significant increase in T-cell receptor-induced cell activation, proliferation and cytokine production. Transgenic T lymphocytes expressing OpIAP have a lower proliferation threshold in response to T-cell receptor stimulation. Unstimulated OpIAP transgenic T lymphocytes show elevated nuclear levels of NF-jB transcription factor that increase after in vivo antigen peptide treatment. OpIAP transgenic animals present an exacerbated inflammatory response in an experimental contact hypersensitivity model, suggesting increased T-cell activation in vivo. These data indicate a new role for the inhibitor of apoptosis proteins in T-lymphocyte activation and proliferation.