CD94 ligation induces apoptosis in a subset of IL-2-stimulated NK cells.
CD94 (Kp43) is a member of the human C-type lectin superfamily encoding type II membrane glycoproteins expressed on NK cells and a subset of T cells. Ligation of CD94 has been shown to either potentiate or inhibit NK cell proliferation and cytolytic effector function. Here we show that CD94 ligation triggers apoptosis in IL-2-primed NK cells. Evidence for CD94-induced apoptosis includes: 1) chromatin condensation as measured by increased fluorescence of Hoechst dye, 2) induction of DNA fragmentation, and 3) characteristic morphology by transmission electron microscopy. IL-2 priming (at least 12 h) is required for activation-induced NK cell death triggered by CD94. Activation-induced NK cell death triggered by CD94 ligation is extremely rapid (DNA fragmentation is first observed at 120 min). Unlike activation-induced T cell death, it is not inhibited by neutralizing Abs reactive with TNF-alpha or Fas ligand. Our results suggest that CD94 may play a role in the elimination of activated NK cells during the transition from the innate to the Ag-specific immune response.
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Division of Tumor Immunology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Robertson
M J
MJ
Voss
S
S
Ritz
J
J
Anderson
P
P
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology*; D002449:Cell Aggregation; D002460:Cell Line; D053938:DNA Fragmentation; D018076:DNA, Complementary / Q000235:genetics; D053222:Fas Ligand Protein; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects*; D007700:Kinetics; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018076:DNA, Complementary; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007376:Interleukin-2; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011994:Recombinant Proteins