Abstract
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-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 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes
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CD8-Positive T-Lymphocytes
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Carrier Proteins / metabolism*
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Cell Differentiation
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Cytokines / biosynthesis
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Immunoglobulin E / biosynthesis
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Interferon-gamma / biosynthesis
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Intracellular Signaling Peptides and Proteins*
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Leishmaniasis, Cutaneous / immunology
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Liver / immunology
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Lymphocytic Choriomeningitis / immunology
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Lymphoproliferative Disorders / etiology
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Mice
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Mice, Mutant Strains
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Signal Transduction
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Signaling Lymphocytic Activation Molecule Associated Protein
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Spleen / immunology
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T-Lymphocytes / immunology*
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T-Lymphocytes / virology*
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Th2 Cells / cytology
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Th2 Cells / immunology*
Substances
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Carrier Proteins
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Cytokines
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Intracellular Signaling Peptides and Proteins
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Sh2d1a protein, mouse
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Signaling Lymphocytic Activation Molecule Associated Protein
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Immunoglobulin E
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Interferon-gamma