Regulation of FasL expression in natural killer cells.
Fas ligand (FasL)-mediated cytotoxicity is initiated in natural killer (NK) cells through ligation of their activating receptors. The CD16 receptor has been shown to induce FasL expression and cytotoxicity in NK cells. In this study, we made the novel observation that FasL expression was upregulated in NKL cells stimulated through 2B4 and LFA-1 activating receptors, implying a role for FasL-mediated cytotoxicity early in the immune response. Coligation with CD94/NKG2A human leukocyte antigen (HLA) class I inhibitory receptor did not block the induced FasL expression; therefore, these opposing pathways appear to function independently. We also showed, however, that FasL-mediated cytotoxicity was downregulated in CD94/NKG2A-expressing LAK cells in response to the HLA-E ligand, suggesting a mechanism by which aberrant cells expressing class I may evade FasL-mediated cytotoxicity. Thus we show for the first time that 2B4, LFA-1, and CD94/NKG2A receptors are involved in modulating FasL expression and, therefore, cytotoxicity mediated by NK cells.
Chua
Hui Lin
HL
Department of Microbiology/Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
Serov
Youri
Y
Brahmi
Zacharie
Z
D015703:Antigens, CD / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology; D016172:DNA Fingerprinting; D053938:DNA Fragmentation; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D019169:Jurkat Cells; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic / Q000276:immunology; D000071176:Signaling Lymphocytic Activation Molecule Family; D015854:Up-Regulation; D019014:fas Receptor / Q000276:immunology
D015703:Antigens, CD; C084093:CD244 protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015234:HLA-A Antigens; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D019014:fas Receptor