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

• Published in: The Journal of immunology (1950) Vol. 158; no. 3; pp. 1262 - 1267
• Main Authors: Ortaldo, JR, Mason, AT, Mason, LH, Winkler-Pickett, RT, Gosselin, P, Anderson, SK
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.02.1997
• Subjects: Animals; Blood Proteins - physiology; Cytotoxicity, Immunologic; H-2 Antigens - immunology; Histocompatibility Antigens Class I - immunology; HLA-C Antigens - immunology; Humans; Immunity, Cellular; Killer Cells, Natural - immunology; Mice; Mice, Inbred C57BL; Neoplasms - immunology; Receptors, Immunologic - immunology; Receptors, Natural Killer Cell; RNA, Antisense; Transfection
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.158.3.1262

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.