Cytokine regulation of cell-to-cell interactions in lymphokine-activated killer cell cytotoxicity in vitro


The permanent pancreas carcinoma cell line, PCI-24, was developed in order to analyse cytokine regulation on pancreas carcinoma and lymphokine-activated killer (LAK) cell interaction. PCI cells expressed ICAM-1 and HLA-ABC, but not HLA-DR antigens. PCI cells showed augmented ICAM-1 and HLA-ABC expression when incubated with interferon γ (IFNγ) and tumour necrosis factor α. A similar but weak augmentary effect on the HLA-ABC and ICAM-1 surface expression was seen with interleukin-1β treatment. Natural attachment of LAK to PCI cells was augmented by recombinant IFNγ in close association with ICAM-1 up-regulation on PCI cells. In addition, natural attachment was significantly inhibited by anti-LFA-1 and anti-ICAM-1 antibody treatments. Cytotoxicity of the LAK cells against PCI cells was also significantly inhibited with the same treatment. Thus, the attachment of LAK cells to PCI cells through LFA-1/ICAM-1 molecules appeared to be essential for the cytotoxicity for PCI cells. Pretreatment of PCI cells, but not of LAK cells, with IFNγ or other cytokines resulted in a decrease of susceptibility for LAK cell cytotoxicity. The decreased susceptibility inversely correlated with HLA-ABC expression on the PCI cells. The collective evidence indicates that, although LAK cell attachment to pancreas carcinoma cells through the LFA-1/ICAM-1 molecule is augmented by IFNγ, IFNγ treatment of pancreas carcinoma cells reduces LAK cell cytotoxicity possibly through an increase in HLA-ABC or a regulation of molecules closely associated to HLA-ABC expression.

DOI: 10.1007/BF01754405

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@article{Takahashi1993CytokineRO, title={Cytokine regulation of cell-to-cell interactions in lymphokine-activated killer cell cytotoxicity in vitro}, author={Toshiyuki Takahashi and Hiroshi Ishikura and Kazuhiro Iwai and Chisa Takahashi and H. Kato and Tatsuzo Tanabe and Takashi Yoshiki}, journal={Cancer Immunology, Immunotherapy}, year={1993}, volume={36}, pages={76-82} }