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Cutting Edge |
* Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, St. Andrews Place, East Melbourne, Victoria, Australia; and
Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, CA 94720
We have investigated the primary immunity generated in vivo by
MHC class I-deficient and -competent tumor cell lines that expressed
the NKG2D ligand retinoic acid early inducible-1 (Rae-1) 
.
Rae-1 expression on class I-deficient RMA-S lymphoma cells enhanced
primary NK cell-mediated tumor rejection in vivo, whereas RMA-Rae-1
tumor cells were rejected by a combination of NK cells and
CD8+ T cells. Rae-1 expression stimulated NK cell
cytotoxicity and IFN-
secretion in vitro, but not proliferation.
Surprisingly, only NK cell perforin-mediated cytotoxicity, but not
production of IFN-, was critical for the rejection of
Rae-1-expressing tumor cells in vivo. This distinct requirement for
perforin activity contrasts with the NK cell-mediated rejection of MHC
class I-deficient RMA-S tumor cells expressing other activating ligands
such as CD70 and CD80. Thus, these results indicated that NKG2D acted
as a natural cytotoxicity receptor to stimulate perforin-mediated
elimination of ligand-expressing tumor cells.
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J. Regunathan, Y. Chen, D. Wang, and S. Malarkannan NKG2D receptor-mediated NK cell function is regulated by inhibitory Ly49 receptors Blood, January 1, 2005; 105(1): 233 - 240. [Abstract] [Full Text] [PDF]
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M. J. Smyth, J. Swann, J. M. Kelly, E. Cretney, W. M. Yokoyama, A. Diefenbach, T. J. Sayers, and Y. Hayakawa NKG2D Recognition and Perforin Effector Function Mediate Effective Cytokine Immunotherapy of Cancer J. Exp. Med., November 15, 2004; 200(10): 1325 - 1335. [Abstract] [Full Text] [PDF]
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S. Radhakrishnan, L. T. Nguyen, B. Ciric, D. Flies, V. P. V. Keulen, K. Tamada, L. Chen, M. Rodriguez, and L. R. Pease Immunotherapeutic Potential of B7-DC (PD-L2) Cross-Linking Antibody In Conferring Antitumor Immunity Cancer Res., July 15, 2004; 64(14): 4965 - 4972. [Abstract] [Full Text] [PDF]
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J. Brady, Y. Hayakawa, M. J. Smyth, and S. L. Nutt IL-21 Induces the Functional Maturation of Murine NK Cells J. Immunol., February 15, 2004; 172(4): 2048 - 2058. [Abstract] [Full Text] [PDF]
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J. A. Westwood, J. M. Kelly, J. E. Tanner, M. H. Kershaw, M. J. Smyth, and Y. Hayakawa Cutting Edge: Novel Priming of Tumor-Specific Immunity by NKG2D-Triggered NK Cell-Mediated Tumor Rejection and Th1-Independent CD4+ T Cell Pathway J. Immunol., January 15, 2004; 172(2): 757 - 761. [Abstract] [Full Text] [PDF]
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A. P. Junqueira-Kipnis, A. Kipnis, A. Jamieson, M. G. Juarrero, A. Diefenbach, D. H. Raulet, J. Turner, and I. M. Orme NK Cells Respond to Pulmonary Infection with Mycobacterium tuberculosis, but Play a Minimal Role in Protection J. Immunol., December 1, 2003; 171(11): 6039 - 6045. [Abstract] [Full Text] [PDF]
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M. J. Smyth, S. E. A. Street, and J. A. Trapani Cutting Edge: Granzymes A and B Are Not Essential for Perforin-Mediated Tumor Rejection J. Immunol., July 15, 2003; 171(2): 515 - 518. [Abstract] [Full Text] [PDF]
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