Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP
MJ Czar, EN Kersh, LA Mijares… - Proceedings of the …, 2001 - National Acad Sciences
MJ Czar, EN Kersh, LA Mijares, G Lanier, J Lewis, G Yap, A Chen, A Sher, CS Duckett…
Proceedings of the National Academy of Sciences, 2001•National Acad SciencesWe have introduced a targeted mutation in SH2D1A/DSHP/SAP, the gene responsible for
the human genetic disorder X-linked lymphoproliferative disease (XLP). SLAM-associated
protein (SAP)-deficient mice had normal lymphocyte development, but on challenge with
infectious agents, recapitulated features of XLP. Infection of SAP− mice with lymphocyte
choriomeningitis virus (LCMV) or Toxoplasma gondii was associated with increased T cell
activation and IFN-γ production, as well as a reduction of Ig-secreting cells. Anti-CD3 …
the human genetic disorder X-linked lymphoproliferative disease (XLP). SLAM-associated
protein (SAP)-deficient mice had normal lymphocyte development, but on challenge with
infectious agents, recapitulated features of XLP. Infection of SAP− mice with lymphocyte
choriomeningitis virus (LCMV) or Toxoplasma gondii was associated with increased T cell
activation and IFN-γ production, as well as a reduction of Ig-secreting cells. Anti-CD3 …
We have introduced a targeted mutation in SH2D1A/DSHP/SAP, the gene responsible for the human genetic disorder X-linked lymphoproliferative disease (XLP). SLAM-associated protein (SAP)-deficient mice had normal lymphocyte development, but on challenge with infectious agents, recapitulated features of XLP. Infection of SAP− mice with lymphocyte choriomeningitis virus (LCMV) or Toxoplasma gondii was associated with increased T cell activation and IFN-γ production, as well as a reduction of Ig-secreting cells. Anti-CD3-stimulated splenocytes from uninfected SAP− mice produced increased IFN-γ and decreased IL-4, findings supported by decreased serum IgE levels in vivo. The Th1 skewing of these animals suggests that cytokine misregulation may contribute to phenotypes associated with mutation of SH2D1A/SAP.
National Acad Sciences