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Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP
Open accessAbstract
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.
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Citations
Cited by
Cellular responses to viral infection in humans: lessons from Epstein–Barr virus
Hislop, A. D., Taylor, G. S., Sauce, D., & Rickinson, A. B. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141553 · Cited by 766
SAP-controlled T–B cell interactions underlie germinal centre formation
Qi, H., Cannons, J. L., Klauschen, F., Schwartzberg, P. L., & Germain, R. N. (2008) · Nature · doi:10.1038/nature07345 · Cited by 637
Self-citationRegulation of NKT cell development by SAP, the protein defective in XLP
Nichols, K. E., Hom, J., Gong, S.-Y., Ganguly, A., Ma, C. S., Cannons, J. L., Tangye, S. G., Schwartzberg, P. L., Koretzky, G. A., & Stein, P. L. (2005) · Nature Medicine · doi:10.1038/nm1189 · Cited by 391
Self-citationHarker, J. A., Lewis, G. M., Mack, L., & Zuniga, E. I. (2011) · Science · doi:10.1126/science.1208421 · Cited by 311
Th2 Cells: Orchestrating Barrier Immunity
(2004) · Advances in Immunology · doi:10.1016/s0065-2776(04)83005-0 · Cited by 44
Metadata
- Authors
- Czar, M. J., Kersh, E. N., Mijares, L. A., Lanier, G., Lewis, J., Yap, G., Chen, A., Sher, A., Duckett, C. S., Ahmed, R., & Schwartzberg, P. L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2001-06-12
- Volume
- 98
- Issue
- 13
- Pages
- 7449-7454
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2142746570
- Cited by
- 260
- References
- 0
- FWCI
- 5.92
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP. https://app.cochat.ai/papers/10.1073/pnas.131193098
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- Czar, M. J., Kersh, E. N., Mijares, L. A., Lanier, G., Lewis, J., Yap, G., Chen, A., Sher, A., Duckett, C. S., Ahmed, R., & Schwartzberg, P. L. (2001). Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.131193098
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
