SAP controls T cell responses to virus and terminal differentiation of TH2 cells


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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Figure 1: Targeted disruption of the gene encoding SAP, Sh2d1a.
Figure 2: Immune responses of SAP-deficient mice to LCMV infection.
Figure 3: Analysis of cytokine production in SAP-deficient T and NKT cells.
Figure 4: SAP-deficient mice are resistant to L. major infection.
Figure 5: Defective IgE production in SAP-deficient mice.


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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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Correspondence to Cox Terhorst.

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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).

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