© 2004 by Society
© 2004 by the Society forNeuro-Oncology
Interactions of the allogeneic effector leukemic T cell line, TALL-104,with human malignant brain tumors
Departments of Pathology (G.G.G., L.E.G.,C.A.K.), Immunology (S.B.R., A.Z., C.A.K.), and Physiology (A.Z.), University of Colorado Health SciencesCenter, Denver, CO 80262, and The Wistar Institute(D.S.), Philadelphia, PA 19104; USA
2 Address correspondence to Carol A. Kruse, Department of Immunology, Campus BoxB216, University of Colorado Health Sciences Center, 4200 East Ninth Avenue,Denver, CO 80262(carol.kruse{at}uchsc.edu).
| Abstract |
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TALL-104 is a human leukemic T cell line that expresses markerscharacteristic of both cytotoxic T lymphocytes and natural killer cells.TALL-104 cells are potent tumor killers, and the use of lethally irradiatedTALL-104 as cellular therapy for a variety of tumors has been explored. Weinvestigated the interactions of TALL-104 cells with human brain tumor cells.TALL-104 cells mediated increased lysis of a panel of brain tumor cells at loweffector-to-target ratios over time. We obtained evidence that TALL-104 cellsinjured glioma cells by both apoptotic and necrotic pathways. A 7-aminoactinomycin D flow cytometry assay revealed that the percentages of bothapoptotic and necrotic glioma cells increased after TALL-104 cell/glioma cellcoincubations. Fluorescent microscopy studies and a quantitative morphologicassay confirmed that TALL-104 cell/glioma cell interactions resulted in tumorcell apoptosis. Cytokines are secreted when TALL-104 cells are coincubatedwith brain tumor cells; however, morphologic analysis assays revealed that thesoluble factors contained within clarified supernates obtained from 4 hcoincubates added back to brain tumor cell cultures did not trigger the gliomaapoptosis. TALL-104 cells do not express Fas ligand, even upon coincubationwith glioma targets, which suggests that the Fas/Fas ligand apoptotic pathwayis not likely responsible for the cell injury observed. We obtained evidencethat cell injury is calcium dependent and that lytic granule exocytosis istriggered by contact of TALL-104 cells with human glioma cells, suggestingthat this pathway mediates glioma cell apoptosis and necrosis.
Received April 23, 2003; Accepted October 10, 2003