Results

We found that this phenomenon was associated with the different susceptibility of human and mouse NK cells to autologous tumour cell-induced NK cell abnormalities (NKCA). The latter includes CD16 down-regulation and NK cell depletion. Induction of NKCA by leukaemia and solid tumour cells was influenced neither by IL2 treatment nor by HLA class I antigen expression, but was abrogated by a 10 day culture. Following a 10 day of PBMCs culture, NK cells became resistant to leukaemia and solid tumor cell induced NKCA but maintained their cytotoxic activity. Actinomycin D restored the susceptibility of long term NK (LTNK) cells to NKCA suggesting that the generation of resistance to NKCA required RNA transcription. TAPI-0, a functional analogue of the tissue inhibitor of metalloproteinases (TIMP) 3 inhibited cancer cell induced NKCA underlying a role for a restricted number of metalloproteinases in the generation of this phenomenon. Finally, we found an association of TIMP3 gene and protein over-expression with the reduced susceptibility of LTNK cells to cancer cell induced NKCA.