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Interactions
of the allogeneic effector leukemic T cell line, TALL-104, with human malignant
brain tumors
German
G. Gomez, Susana B. Read, Lazaro E. Gerschenson, Daniela Santoli, Adam Zweifach,
Carol A. Kruse
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
Sciences Center, Denver, CO 80262, and The Wistar Institute (D.S.),
Philadelphia, PA 19104; USA
TALL-104
is a human leukemic T cell line that expresses markers characteristic of both
cytotoxic T lymphocytes and natural killer cells.
TALL-104 cells are potent tumor killers, and the use of lethally irradiated
TALL-104 as cellular therapy for a variety of tumors has been explored.
We investigated the interactions of TALL-104 cells with human brain tumor
cells.
TALL-104 cells mediated in creased lysis of a panel of brain tumor cells at low
effector-to-target ratios over time.
We obtained evidence that TALL-104 cells injured glioma cells by both apoptotic
and necrotic pathways.
A 7-amino actinomycin D flow cytometry assay revealed that the percentages of
both apoptotic and necrotic glioma cells increased after TALL-104 cell/glioma
cell coincubations.
Fluorescent microscopy studies and a quantitative morphologic assay confirmed
that TALL-104 cell/glioma cell interactions resulted in tumor cell
apoptosis.
Cytokines are secreted when TALL-104 cells are coincubated with brain tumor
cells; however, morphologic analysis assays revealed that the soluble factors
contained within clarified supernates obtained from 4 h coincubates added back
to brain tumor cell cultures did not trigger the glioma apoptosis.
TALL-104 cells do not express Fas ligand, even upon coincubation with glioma
targets, which suggests that the Fas/Fas ligand apoptotic pathway is not likely
responsible for the cell injury observed.
We obtained evidence that cell injury is calcium dependent and that lytic
granule exocytosis is triggered by contact of TALL-104 cells with human glioma
cells, suggesting that this pathway mediates glioma cell apoptosis and necrosis.
©
2004 Duke University Press
Source:
http://konstanza.ingentaselect.com/vl=4164418/cl=19/nw=1/rpsv/cgi-bin/linker?ini=dup_no&reqidx=/cw/dup/15228517/v6n2/s1/p83
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