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 (NR) cells into CD2(-) CD5 6(dim) (CD2(-) NK), CD2(+) CD56(dim) (CD2(+) NK) and CD2(+) CD56(brigh t) 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 co rd blood and bone marrow than in the peripheral blood of adults or chi ldren. 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 app ears on the surface during the maturation of NK cells. The granule-med iated cytotoxicities, which are mainly performed by the perforin molec ule, 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 antibod y (mAb). Fas ligand (Fast) mRNA was expressed in freshly isolated CD2( +) NK cells but not in the CD2(-) NK cells. Neither freshly isolated N K populations showed FasL-mediated cytotoxicity, and only CD2(+) NE( c ells lysed Fas-transfected targets after the 24-hr incubation with IL- 2, Based on these results, CD2(-) NK cells have already developed gran ule-mediated cytotoxicity equal to that of CD2(+) NK cells except for the CD2-associated activity, but they, unlike CD2(+) NK tells, totally lack Fast-mediated cytotoxicity. These findings suggest that Fast-med iated cytotoxicity may be acquired at more mature stages of NK-cell ma turation than granule-mediated cytotoxicity.