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

Nat Immunol. 2001 May;2(5):410-4. doi: 10.1038/87713.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Carrier Proteins / metabolism*
  • Cell Differentiation
  • Cytokines / biosynthesis
  • Immunoglobulin E / biosynthesis
  • Interferon-gamma / biosynthesis
  • Intracellular Signaling Peptides and Proteins*
  • Leishmaniasis, Cutaneous / immunology
  • Liver / immunology
  • Lymphocytic Choriomeningitis / immunology
  • Lymphoproliferative Disorders / etiology
  • Mice
  • Mice, Mutant Strains
  • Signal Transduction
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Spleen / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology*
  • Th2 Cells / cytology
  • Th2 Cells / immunology*


  • Carrier Proteins
  • Cytokines
  • Intracellular Signaling Peptides and Proteins
  • Sh2d1a protein, mouse
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Immunoglobulin E
  • Interferon-gamma