SAP controls T cell responses to virus and terminal differentiation of T(H)2 cells

SH2DIA, which encodes signaling lymphocyte activation molecule (SLAM)-assoc iated protein (SAP), is altered in patients with X-linked lymphoproliferati ve disease (XLP), a primary immunodeficiency, SAP-deficient mice infected w ith lymphocytic choriomeningitis virus had greatly increased numbers of CD8 (+) and CD4(+) interferon-gamma -producing spleen and liver cells compared to wild-type mice. The immune responses of SAP-deficient mice to infection with Leishmania major together with in vitro studies showed that activated SAP-deficient T cells had an impaired ability to differentiate into T helpe r 2 cells,The aberrant immune responses in SAP-deficient mice show that SAP controls several distinct key T cell signal transduction pathways, which e xplains in pare the complexity of the XLP phenotypes.