Signaling lymphocytic activation molecule-associated protein controls NKT cell functions

Brian Chung; Ala Aoukaty; Jan Dutz; Cox Terhorst; Rusung Tan

doi:10.4049/jimmunol.174.6.3153

Signaling lymphocytic activation molecule-associated protein controls NKT cell functions

J Immunol. 2005 Mar 15;174(6):3153-7. doi: 10.4049/jimmunol.174.6.3153.

Authors

Brian Chung¹, Ala Aoukaty, Jan Dutz, Cox Terhorst, Rusung Tan

Affiliation

¹ Department of Pathology and Laboratory Medicine, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.

PMID: 15749842
DOI: 10.4049/jimmunol.174.6.3153

Abstract

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, alpha-galactosylceramide failed to generate NKT cell IFN-gamma or IL-4. Furthermore, in contrast to wild-type littermates, SAPKO mice coinjected with OVA and alpha-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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, CD1 / metabolism
Antigens, CD1d
Cytokines / biosynthesis
Galactosylceramides / immunology
Galactosylceramides / pharmacology
Humans
Intracellular Signaling Peptides and Proteins / deficiency
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / immunology*
Killer Cells, Natural / drug effects
Killer Cells, Natural / immunology*
Lymphocyte Activation
Lymphoproliferative Disorders / genetics
Lymphoproliferative Disorders / immunology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutation
Signaling Lymphocytic Activation Molecule Associated Protein
T-Lymphocyte Subsets / drug effects
T-Lymphocyte Subsets / immunology*
T-Lymphocytes, Cytotoxic / immunology

Substances

Antigens, CD1
Antigens, CD1d
CD1D protein, human
Cytokines
Galactosylceramides
Intracellular Signaling Peptides and Proteins
SH2D1A protein, human
Sh2d1a protein, mouse
Signaling Lymphocytic Activation Molecule Associated Protein