Enhanced generation of NK cells with intact cytotoxic function in CD45 exon 6-deficient mice.

Abstract

CD45 is a cell membrane-type protein tyrosine phosphatase that is essential for Ag receptor-mediated signaling in both T and B lymphocytes. To characterize roles of CD45 molecules in murine NK cells, we analyzed the development and the cytotoxic functions of NK cells in mice lacking CD45 exon 6 (CD45 -/-). A markedly increased number of NK cells was observed in spleens of the CD45 -/- mice, despite no CD45 surface expression on the NK cells. From the results of mixed bone marrow chimera experiments, it was demonstrated that the expansion of NK cells in CD45 -/- mice was due to the influence of disappeared expression of CD45 in the NK cells per se, but not to the modulation of environmental factors. The NK cells in the CD45 -/- mice had normal cytotoxic activities, including NK and Ab-dependent cell-mediated cytotoxicity activities comparable with those in normal mice (CD45 +/+). Additionally, the CD45 -/- NK cells could functionally differentiate to lymphokine-activated killer cells by culturing with a high dose of IL-2, despite a lack of induced expression of B220. Therefore, these results suggest that CD45 is involved in NK cell development, but is not essential for cytotoxic activities and Fc gamma R-mediated signaling in NK cells.