Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP

Michael J. Czar, Ellen N. Kersh, Lilia A. Mijares, Gibson Lanier, Jennifer Lewis, George Yap, Amy Chen, Alan Sher, Colin S. Duckett, Rafi Ahmed, Pamela L. Schwartzberg

Research output: Contribution to journalArticlepeer-review

218 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7449-7454
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number13
DOIs
StatePublished - Jun 19 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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