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The Journal of Immunology, Vol 158, Issue 3 1262-1267, Copyright © 1997 by American Association of Immunologists


ARTICLES

Selective inhibition of human and mouse natural killer tumor recognition using retroviral antisense in primary natural killer cells: involvement with MHC class I killer cell inhibitory receptors

JR Ortaldo, AT Mason, LH Mason, RT Winkler-Pickett, P Gosselin and SK Anderson
Laboratory of Experimental Immunology, National Cancer Institute, Frederick, MD 21702, USA.

The natural killer tumor recognition (NK-TR) protein has been shown to be a necessary component for the killing of NK-sensitive and virus- infected targets by the rat RNK-16 cell line. Class I-recognizing killer cell inhibitory receptors (KIR) have been found in the human (p58; NKAT family) and mouse (Ly-49 family). The principal functional characteristic of these receptors is their ability to block NK cell lysis by recognition of selected class I molecules on target cells. In the present study, we examined whether abrogation of NK-TR expression by retroviral infection of primary human or mouse NK cells with virus- producing antisense NK-TR also would demonstrate loss of non-MHC- restricted killing and whether the NK-TR was associated with KIR function in humans or with Ly-49 in the mouse. Using short term culture of fresh human or mouse NK cells, antisense NK-TR-treated NK cells demonstrated strong selective reduction of NK cytotoxicity. NK-TR was necessary for lytic activity even when KIR function was blocked by Ab in experiments involving NK3.3 lysis of HLA.cw3-expressing targets or killing of Dd targets by Ly-49A+ or Ly-49G2+ mouse NK cells. These studies extend our previous studies in rat NK cell lines to demonstrate that primary mouse and human NK cells require NK-TR for non-MHC- restricted lysis of tumor and virus-infected targets. In addition, the reversal of KIR or Ly-49 inhibition of NK cell lysis requires NK-TR expression for cellular killing in both human and mouse.


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