SAP controls T cell responses to virus and terminal differentiation of TH2 cells.
SH2D1A, which encodes signaling lymphocyte activation molecule (SLAM)-associated protein (SAP), is altered in patients with X-linked lymphoproliferative disease (XLP), a primary immunodeficiency. SAP-deficient mice infected with lymphocytic choriomeningitis virus had greatly increased numbers of CD8+ and CD4+ interferon-gamma-producing spleen and liver cells compared to wild-type mice. The immune responses of SAP-deficient mice to infection with Leishmania major together with in vitro studies showed that activated SAP-deficient T cells had an impaired ability to differentiate into T helper 2 cells. The aberrant immune responses in SAP-deficient mice show that SAP controls several distinct key T cell signal transduction pathways, which explains in part the complexity of the XLP phenotypes.
Wu
C
C
Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Nguyen
K B
KB
Pien
G C
GC
Wang
N
N
Gullo
C
C
Howie
D
D
Sosa
M R
MR
Edwards
M J
MJ
Borrow
P
P
Satoskar
A R
AR
Sharpe
A H
AH
Biron
C A
CA
Terhorst
C
C
D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins; D016773:Leishmaniasis, Cutaneous / Q000276:immunology; D008099:Liver / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000209:etiology; D051379:Mice; D008817:Mice, Mutant Strains; D015398:Signal Transduction; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
D002352:Carrier Proteins; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; C499569:Sh2d1a protein, mouse; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D007073:Immunoglobulin E; D007371:Interferon-gamma