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

Abstract

SUMMARYWe 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 bone 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 FasLmediated 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 granulemediated 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.

Notch Regulates Cytolytic Effector Function in CD8+ T Cells

“…During the course of an infection, two distinct pathways regulate the cytolytic function of both NK and CD8 + T cells; namely granule exocytosis and Fas-FasL interactions (25, 26). The granule exocytosis pathway uses the pore-forming molecule, perforin and the protease, granzymes B, whereas the Fas-FasL pathway facilitates programmed cell death by aggregation of Fas (CD95) on target cells.…”

NK and NKT cell functions in immunosenescence

“…Mature NK cells are characterized by the expression of peculiar markers such as CD56, an isoform of the neural cell adhesion molecule (N-CAM), CD16, the low-affinity IgG Fc receptor (FcR γ IIIA), CD57, an oligosaccharide antigenic determinant, and CD2, an adhesion molecule that appears to be correlated with the acquisition of fas ligand-mediated cytotoxicity (Nakazawa et al ., 1997).…”

T cells expressing the γδ receptor are essential for Th2‐mediated inflammation in patients with acute exacerbation of asthma

“…Recent studies reported that NK cells in the inflammatory sites operate through the Fas/FasL interaction, and that FasL was expressed in the inflammatory sites. 28 Interestingly mononuclear cells co-expressed both Fas and FasL, suggesting that Fas/ FasL interactions may function in not only a paracrine way, but also an autocrine way. This may be relevant to the abnormal immune response in diseases.…”