NK cytokine secretion and cytotoxicity occur independently of the SLP-76 adaptor protein

Erik J. Peterson, James L. Clements, Zuhair K. Ballas, Gary A. Koretzky

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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-γ 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 FcγRIIIA (which mediates antibody-dependent cellular cytotoxicity), and by natural cytotoxicity-associated receptors on murine NK cells can occur independently of SLP-76.

Original languageEnglish (US)
Pages (from-to)2223-2232
Number of pages10
JournalEuropean Journal of Immunology
Issue number7
StatePublished - 1999


  • Cytotoxicity
  • Knockout
  • NK cell
  • Transgenic


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