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Blood, 1 October 2004, Vol. 104, No. 7, pp. 2116-2123.
Prepublished online as a Blood First Edition Paper on June 3, 2004; DOI 10.1182/blood-2004-01-0150.
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Submitted January 14, 2004
Accepted May 13, 2004
Self-Reactive Memory-Phenotype CD8 T Cells Exhibit Both MHC-Restricted and Non-MHC Restricted Cytotoxicity: A Role for the T Cell Receptor and Natural Killer Cell Receptors
Salim Dhanji, Soo-Jeet Teh, Darryl Oble, John J Priatel, and Hung-Sia Teh*
Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
* Corresponding author; email: teh{at}interchange.ubc.ca.
We have recently shown that IL-2-activated CD8+CD44hi cells from normal mice express both adaptive and innate immune system receptors and specifically kill syngeneic tumor cells, particularly those that express NKG2D ligands. Here we show that CD8+ T cells from antigen-expressing H-Y TCR transgenic mice also exhibit characteristics of both T cells and NK cells. Interaction with cognate self-antigen was required for the optimal expansion of these cells in peripheral lymphoid tissues. Although these cells possess a higher activation threshold relative to naive T cells, they can be activated by cytokine alone in vitro. They also undergo bystander proliferation in response to a bacterial infection in vivo. Interestingly, upon activation, the cells express the NKG2D receptor as well as the DAP12 adaptor protein. We provide evidence that NKG2D can act additively with the TCR in the killing of target cells and it can also function as a directly activating receptor in non-MHC restricted killing of target cells. These properties of CD8+ T cells from H-Y TCR transgenic mice are remarkably similar to CD8+CD44hi cells that are found in normal mice. The H-Y TCR transgenic mice provide a well-defined system for characterizing the developmental biology and function of these cells.

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