SH2D1A, which encodes signaling lymphocyte activation molecule (SLAM)–associated protein (SAP), is altered in patients with X-linked lymphoproliferative disease (XLP), a primary immunodeficiency. SAP-deficient mice infected with lymphocytic choriomeningitis virus had greatly increased numbers of CD8+ and CD4+ interferon-γ–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 helper 2 cells. The aberrant immune responses in SAP-deficient mice show that SAP controls several distinct key T cell signal transduction pathways, which explains in part the complexity of the XLP phenotypes.
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We thank L. Du and J. Burgess for their technical assistance in generating the SAP−/− mice; O. Leo, A. Bhan and S. Ju for their technical advice; J. Fingeroth, N. Houten and Y. Jong for a critical review of the manuscript and the NIAID Tetramer Facility, NIH AIDS Research and Reference Reagent Program and J. Altman for providing the LCMV tetramers. Supported by the Cancer Research Institute (C. W.), the Leukemia Society (D. H.) and grants from the NIH.
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Wu, C., Nguyen, K., Pien, G. et al. SAP controls T cell responses to virus and terminal differentiation of TH2 cells. Nat Immunol 2, 410–414 (2001). https://doi.org/10.1038/87713
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