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X-linked lymphoproliferative disease (XLP): a model of impaired anti-viral, anti-tumor and humoral immune responses

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Abstract

A major focus of our research is to understand the molecular and cellular basis of X-linked lymphoproliferative disease (XLP), a rare and often fatal immunodeficiency caused by mutations in the SH2D1A gene, which encodes the adaptor molecule SAP. Recently, we observed that SAP is essential for the development of natural killer T (NKT) cells, a lymphocyte population that participates in protection against certain tumors, infections, and autoimmune states. In this review, we describe the approaches that we are taking to understand the role of SAP in immune cells, including NKT cells. By using SAP as the focal point of our studies, we hope to identify novel signaling pathways that could be targeted to improve the treatment for patients with XLP as well as more common disorders, such as autoimmunity and cancer.

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Acknowledgments

We thank Mitchell Kronenberg, Pamela Schwartzberg, Juan Carlos Zuniga-Pflucker, Kirin Brewery, and the National Institutes of Health (NIH) Tetramer Facility for providing reagents. We also thank Justina Stadanlick for editorial assistance with this manuscript. This work was funded by grants from the NIH and the XLP Research Trust.

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Authors and Affiliations

  1. Infectious Diseases Fellowship Training Program, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Hamid Bassiri

  2. Division of Oncology, Children’s Hospital of Philadelphia, Wood Building 4th Floor, Oncology mailbox, 3615 Civic Center Boulevard, Philadelphia, PA, 19104, USA

    W. C. Janice Yeo & Kim E. Nichols

  3. Hematology/Oncology Fellowship Training Program, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Jennifer Rothman

  4. Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Gary A. Koretzky

  5. Abramson Family Cancer Research Institute, Philadelphia, PA, USA

    Gary A. Koretzky

  6. Division of Rheumatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Gary A. Koretzky

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  1. Hamid Bassiri
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Correspondence to Kim E. Nichols.

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Bassiri, H., Janice Yeo, W.C., Rothman, J. et al. X-linked lymphoproliferative disease (XLP): a model of impaired anti-viral, anti-tumor and humoral immune responses. Immunol Res 42, 145–159 (2008). https://doi.org/10.1007/s12026-008-8048-7

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