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CUTTING EDGE |
Departments of
*
Pathology and Laboratory Medicine and
Medicine, British Columbia Children’s Hospital and University of British Columbia, Vancouver, British Columbia, Canada; and
Harvard Institute of Medicine, Boston, MA 02115
X-linked lymphoproliferative disease (XLP) is a fatal immunological disorder that typically manifests following EBV infection. XLP patients exhibit a number of immune defects including abnormal T, B, and NK lymphocyte function. These defects have been attributed to mutations of Src homology 2 domain-containing gene 1A (SH2D1A), the gene encoding signaling lymphocytic activation molecule-associated protein (SAP), an intracellular adaptor molecule expressed in lymphocytes. We have observed that SAP knockout (SAPKO) mice and humans with XLP have a complete lack of CD1d-restricted NKT cells. As expected, SAPKO mice injected with the NKT cell agonist, 
-galactosylceramide failed to generate NKT cell IFN-
or IL-4. Furthermore, in contrast to wild-type littermates, SAPKO mice coinjected with OVA and -galactosylceramide failed to mount OVA-specific CTL responses. These data suggest that an absence of NKT cells may underlie part of the immune dysregulation seen in SAPKO mice and in XLP patients.
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