Cytokine modulation of the susceptibility of acute T-lymphoblastic leukemia cell lines to LAK activity.
We studied the regulatory effects of various cytokines on the susceptibility to lymphocyte-mediated lysis of cell lines established from patients with acute T-lymphoblastic leukemia (T-ALL). None of the cytokines tested affected the sensitivity of these targets to natural killer activity. In contrast, specific cytokines, different for each cell line, enhanced the susceptibility to lymphokine-activated killer (LAK) cells, while interferon gamma (IFN)-gamma always induced resistance. The same cytokines that increased LAK susceptibility also induced proliferative responses. The TALL-101 cell line, which responded to granulocyte-macrophage colony-stimulating factor (GM-CSF) with increased susceptibility to lysis, and to IFN-gamma with resistance, was used as a model to analyze the mechanisms underlying these changes. Cold target inhibition and conjugate formation assays both indicated that the changes in LAK susceptibility were not at the level of effector-target (E/T) binding. Furthermore, no significant changes in surface expression of adhesion molecules involved in E/T binding were induced by either GM-CSF or IFN-gamma on TALL-101 cells. Finally, N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl-esterase assays demonstrated no differences in the ability of these cytokines to trigger the secretion of cytolysins in the bound effectors compared to unstimulated cells. Taken together, these results suggest that the cytokine-modulated susceptibility to lysis of these T-ALL lines might occur at a post-binding stage with mechanisms involving an altered responsiveness to lytic factors.
Cesano
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Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Clark
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SC
Santoli
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D002455:Cell Division / Q000187:drug effects; D002648:Child; D016207:Cytokines / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000502:physiology*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016207:Cytokines; D011948:Receptors, Antigen, T-Cell