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.

Abstract

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.

• Authors: J R Ortaldo, A T Mason, L H Mason, R T Winkler-Pickett, P Gosselin, S K Anderson
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 158 Issue 3 Pg. 1262-7 (Feb 01 1997) ISSN: 0022-1767 [Print] United States
• PMID: 9013968 (Publication Type: Journal Article)

Chemical References

• Blood Proteins
• H-2 Antigens
• HLA-C Antigens
• HLA-C*03 antigen
• Histocompatibility Antigens Class I
• RNA, Antisense
• Receptors, Immunologic
• Receptors, Natural Killer Cell

Topics

• Animals
• Blood Proteins (physiology)
• Cytotoxicity, Immunologic
• H-2 Antigens (immunology)
• HLA-C Antigens (immunology)
• Histocompatibility Antigens Class I (immunology)
• Humans
• Immunity, Cellular
• Killer Cells, Natural (immunology)
• Mice
• Mice, Inbred C57BL
• Neoplasms (immunology)
• RNA, Antisense
• Receptors, Immunologic (immunology)
• Receptors, Natural Killer Cell
• Transfection