Later development of Fas ligand-mediated cytotoxicity as compared with granule-mediated cytotoxicity during the maturation of natural killer cells

Immunology. 1997 Oct;92(2):180-7. doi: 10.1046/j.1365-2567.1997.00343.x.


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.

MeSH terms

  • CD2 Antigens / analysis
  • Cell Culture Techniques
  • Cell Differentiation / immunology
  • Cytoplasmic Granules / immunology*
  • Cytotoxicity, Immunologic*
  • Gene Expression
  • Humans
  • Immunophenotyping
  • Interleukin-2 / immunology
  • Killer Cells, Natural / immunology*
  • Lymphocyte Subsets / immunology
  • RNA, Messenger / genetics
  • Tumor Cells, Cultured / immunology
  • fas Receptor / genetics
  • fas Receptor / immunology*


  • CD2 Antigens
  • Interleukin-2
  • RNA, Messenger
  • fas Receptor