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

doi:10.1073/pnas.131193098

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

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234 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 language	English (US)
Pages (from-to)	7449-7454
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	98
Issue number	13
DOIs	https://doi.org/10.1073/pnas.131193098
State	Published - Jun 19 2001
Externally published	Yes

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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 of the United States of America, 98(13), 7449-7454. https://doi.org/10.1073/pnas.131193098

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

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.",

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

year = "2001",

month = jun,

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doi = "10.1073/pnas.131193098",

language = "English (US)",

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Czar, MJ, Kersh, EN, Mijares, LA, Lanier, G, Lewis, J, Yap, G, Chen, A, Sher, A, Duckett, CS, Ahmed, R & Schwartzberg, PL 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 of the United States of America, vol. 98, no. 13, pp. 7449-7454. https://doi.org/10.1073/pnas.131193098

Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP. / Czar, Michael J.; Kersh, Ellen N.; Mijares, Lilia A. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 13, 19.06.2001, p. 7449-7454.

Research output: Contribution to journal › Article › peer-review

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AU - Czar, Michael J.

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AU - Mijares, Lilia A.

AU - Lanier, Gibson

AU - Lewis, Jennifer

AU - Yap, George

AU - Chen, Amy

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AU - Duckett, Colin S.

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AU - Schwartzberg, Pamela L.

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

Abstract

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