Expression of the NK-TR gene is required for NK-like activity in human T cells.
NK cells lyse target cells without previous immune sensitization. A small subset of T cells also exhibits NK-like activity, which is distinct from TCR-mediated, MHC-restricted, and MHC-unrestricted cytotoxicity. We recently cloned a gene, NK-TR, which is postulated to be part of the NK target-recognition/triggering complex. To determine whether the NK-TR gene product is requisite for NK-like killing, stable antisense transfectants were generated by using a human T cell clone with NK-like activity. Two distinct antisense regions of the sequence were used to generate the transfectants alpha NK-TR and alpha Cyclo. Transfectants lost the ability to lyse NK-sensitive targets but did not lose lectin-mediated cytotoxic activity. This effect was not seen with the control vector transfectant cell line. The loss of NK-like activity by the antisense transfectant alpha NK-TR correlated with the specific decrease in endogenous NK-TR mRNA and protein. These results demonstrate the requirement for the NK-TR protein for NK-like killing. Moreover, the results have important implications for examining developmental relationship between T and NK cells and the possible roles for T cells with NK-like activity in vivo.
Chambers
C A
CA
Division of Molecular Immunology and Neurobiology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Gallinger
S
S
Anderson
S K
SK
Giardina
S
S
Ortaldo
J R
JR
Hozumi
N
N
Roder
J
J
D001483:Base Sequence; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008969:Molecular Sequence Data; D016372:RNA, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic / Q000032:analysis / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
D007378:Interleukins; C081849:NKTR protein, human; D016372:RNA, Antisense; D012333:RNA, Messenger; D011971:Receptors, Immunologic