Comment on “Cutting Edge: CD8+ T Cell Priming in the Absence of NK Cells Leads to Enhanced Memory Responses”

apoptosis in recently activated CD8 1 T cells in an NKG2Dand perforin-dependent manner. This report is in contrast with previous reports showing that T cells express serine protease inhibitors (SPI-6 in mice and PI-9 in humans) during activation and exposure to IFN-g and become resistant to perforin/granzyme-induced apoptosis (2). It is expected that NK cells produce IFN-g upon engagement of the NKG2D receptor, thereby inducing the expression of SPI-6/PI-9 in T cells and rendering them resistant to perforin/granzymemediated apoptosis. The authors determined apoptosis-inducing effects of NK cells indirectly by showing a reduced frequency of T cells in the presence of NK cells rather than by demonstrating more Annexin V-positive T cells. Such a reduced frequency may be due to a decreased proliferation of T cells during the activation process. Other groups have shown positive effects of NK cells during T cell activation. For instance, depletion of the donor’s NK cells abrogated antileukemia effects of the donor’s T cells in the recipient of a stem cell transplant (3). NK cell recovery also preceded engraftment and expansion of the donor’s T cells (4). Soderquest et al. (1) also showed that depletion of NK cells increased memory CD8 1 T cells. Such a result may be due to eliminating the competition between NK cells and T cells for the consumption of endogenous IL-15 rather than conferring a direct effect.