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 gamma (IFN gamma) and tumour necrosis factor alpha. A similar but weak augmentary effect on the HLA-ABC and ICAM-1 surface expression was seen with interleukin-1 beta treatment. Natural attachment of LAK to PCI cells was augmented by recombinant IFN gamma 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 IFN gamma 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 IFN gamma, IFN gamma 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.
Takahashi
T
T
Department of Pathology, Hokkaido University School of Medicine, Sapporo Japan.
Ishikura
H
H
Iwai
K
K
Takahashi
C
C
Kato
H
H
Tanabe
T
T
Yoshiki
T
T
D000368:Aged; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006680:HLA Antigens / Q000032:analysis / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008297:Male; D010190:Pancreatic Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D006680:HLA Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma