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APC-Independent NK Cell Activation

Institute of Immunology, University of Science and Technology of China

Last year, The Journal of Immunology published Kerstin N. Schmidt’s work titled "APC-Independent Activation of NK Cells by the Toll-Like Receptor 3 Agonist Double-Stranded RNA" (1). In this paper there is an unclear issue about NK cell cytotoxicity assay. The effector cells were human purified CD56⁺ NK cells, but the target cells were YAC-1 cells, an NK cell-sensitive murine-derived cell line. We think the appropriate target is human K562 cell line.

View larger version (11K): [in this window] [in a new window]   FIGURE 1. Poly(I:C) stimulation enhances NK cell-mediated cytotoxicity.

1. Schmidt, K. N., B. Leung, M. Kwong, K. A. Zarember, S. Satyal, T. A. Navas, F. Wang, P. J. Godowski. 2004. APC-independent activation of NK cells by the toll-like receptor 3 agonist double-stranded RNA. J. Immunol. 172: 138-143. [Abstract/Free Full Text]

The Authors Respond

Kerstin N. Schmidt^*, Beatrice Leung^*, Mandy Kwong^*, Kol A. Zarember, Sanjeev Satyal, Tony Navas, Fay Wang^* and Paul J. Godowski^*

^* Department of Immunology, Genentech, South San Francisco, CA 94080 Current address: National Institutes of Health/NIAID, Bethesda, MD 20892 Department of Molecular Biology, Genentech, South San Francisco, CA 94080 Current address: Scios Fremont, CA 94555

We reported that human NK cells express TLR3, and that stimulation with TLR-3 agonist poly(I:C) induces APC-independent NK cell activation (R1 ). Specifically, we found that poly(I:C) stimulation leads to up-regulation of CD69, activation of NF-B, production of proinflammatory cytokines, and augmentation of NK-cell mediated cytotoxicity. The latter was demonstrated with two different target cell lines, human Daudi cells and mouse YAC-1 cells.

Dr. Zhongjun Dong suggests that K562 would be the appropriate target cell line to use. We appreciate Dr. Dong’s comment and his interest in analyzing the lysis of other human cell lines, like K562, in addition to Daudi cells.

In alignment with our data in Daudi and YAC-1 cells, our unpublished results show that poly(I:C) stimulation of NK cells significantly enhances lysis of K562 cells (see Fig. 1). The increase in cell lysis is comparable to that reported for other NK cell activators, IFN- (R2 ), IL-2, and IL-12 (R3 ) using K562 as a target cell line.

Furthermore, our findings have been confirmed and extended by A. Moretta’s group, which reported up-regulation of cytolytic activity against tumor cell lines K562 and FO-1, and immature dendritic cells after stimulation with double-stranded RNA (R4 ).

In conclusion, all data available, including lysis of K562 cells, support direct induction of NK cell activation after stimulation of NK cells with a TLR3 agonist.

References

1. Schmidt, K. N., B. Leung, M. Kwong, K. A. Zarember, S. Satyal, T. A. Navas, F. Wang, P. J. Godowski. 2004. APC-independent activation of NK cells by the toll-like receptor 3 agonist double-stranded RNA. J. Immunol. 172: 138-143.
2. Liang, S., H. Wei, R. Sun, Z. Tian. 2003. IFN- regulated NK cell cytotoxicity through STAT1 pathway. Cytokine 23: 190-199. [Medline]
3. Lehmann, C., M. Zeis, L. Uharek. 2001. Activation of natural killer cells with interleukin 2 (IL-2) and IL-12 increases perforin binding and subsequent lysis of tumour cells. British J. of Haematol. 114: 660-665.
4. Sivori, S., M. Falco, M. D. Chiesa, S. Carlomagno, M. Vitale, L. Moretta, A. Moretta. 2004. Proc. Natl. Acad. Sci. USA. 101: 10116-10121. [Abstract/Free Full Text]

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