Later development of Fas ligand-mediated cytotoxicity as compared with granule-mediated cytotoxicity during the maturation of natural killer cells.
We classified CD56+ CD3- natural killer (NK) cells into CD2- CD56dim (CD2- NK), CD2+ CD56dim (CD2+ NK) and CD2+ CD56bright populations, and investigated mainly functional differences between the former two populations. CD2- and CD2+ NK cells were the same in their morphology and several surface molecules except for CD2. The percentages of CD2- NK cells in total NK cells were higher in the cord blood and marrow than in the peripheral blood of adults or children. Freshly isolated CD2- NK cells had CD2 in the cytoplasm, and gradually expressed it on the surface upon incubation with interleukin-2 (IL-2). These results demonstrated that CD2 is an antigen which appears on the surface during the maturation of NK cells. The granule-mediated cytotoxicities, which are mainly performed by the perforin molecule, of CD2+ NK cells against K562 and Daudi cells were higher than those of CD2- NK cells, and they were inhibited to the levels of CD2- NK cells by the addition of a blocking anti-CD2 monoclonal antibody (mAb). Fas ligand (FasL) mRNA was expressed in freshly isolated CD2+ NK cells but not in the CD2- NK cells. Neither freshly isolated NK populations showed FasL-mediated cytotoxicity, and only CD2+ NK cells lysed Fas-transfected targets after the 24-hr incubation with IL-2. Based on these results, CD2- NK cells have already developed granule-mediated cytotoxicity equal to that of CD2+ NK cells except for the CD2-associated activity, but they, unlike CD2+ NK cells, totally lack FasL-mediated cytotoxicity. These findings suggest that FasL-mediated cytotoxicity may be acquired at more mature stages of NK-cell maturation than granule-mediated cytotoxicity.
Nakazawa
T
T
Department of Paediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
Agematsu
K
K
Yabuhara
A
A
D018801:CD2 Antigens / Q000032:analysis; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000276:immunology; D003594:Cytoplasmic Granules / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000276:immunology; D019014:fas Receptor / Q000235:genetics / Q000276:immunology*
D018801:CD2 Antigens; D007376:Interleukin-2; D012333:RNA, Messenger; D019014:fas Receptor