NK cytokine secretion and cytotoxicity occur independently of the SLP-76 adaptor protein.
The adapter protein SLP-76 is required for T cell development and TCR signal transduction. SLP-76 is also expressed in NK cells, yet splenic populations of NK cells develop normally in SLP-76-deficient mice. We examined the effects of SLP-76 deficiency upon cellular activation through studies of NK function in SLP-76(-/-) mice. This study presents evidence that NK populations in both spleen and liver of SLP-76(-/-) mice remain intact. Natural cytotoxic responses of SLP-76(-/-) splenocytes proceed in a manner comparable to those of wild-type control splenocytes. Similar to controls, SLP-76(-/-) splenocytes exhibit enhanced survival and augmented cytotoxic capacity after in vitro culture with IL-2. IL-2-stimulated SLP-76(-/-) splenocytes also retain normal antibody-dependent cellular cytotoxicity and the ability to secrete IFN-gamma in response to IL-12 stimulation. These results indicate that, unlike events stimulated by TCR engagement, signaling cascades engaged by IL-2 and IL-12 receptors, by Fc gammaRIIIA (which mediates antibody-dependent cellular cytotoxicity), and by natural cytotoxicity-associated receptors on murine NK cells can occur independently of SLP-76.
Peterson
E J
EJ
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Clements
J L
JL
Ballas
Z K
ZK
Koretzky
G A
GA
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D016207:Cytokines / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D007376:Interleukin-2; D010750:Phosphoproteins; C092947:SLP-76 signal Transducing adaptor proteins; D018664:Interleukin-12; D007371:Interferon-gamma