Nature Immunology
2, 410 - 414 (2001)
doi:10.1038/87713
SAP controls T cell responses to virus and terminal differentiation of TH2 cellsChengbin Wu1, Khuong B. Nguyen2, Gary C. Pien2, Ninghai Wang1, Charles Gullo1, Duncan Howie1, Miriam Rodriguez Sosa3, Matthew J. Edwards4, Persephone Borrow4, Abhay R. Satoskar3, Arlene H. Sharpe5, Christine A. Biron2
& Cox Terhorst11
Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. 2
Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA. 3
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA. 4
Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, UK. 5
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Correspondence should be addressed to Cox Terhorst terhorst@caregroup.harvard.edu
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- −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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