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The effect of desferrithiocin, an oral iron chelator, on T-cell function
BE Bierer and DG Nathan
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA
02115.
Desferrithiocin is a new, potent, orally available iron chelator. To
determine whether this drug might be useful not only for iron-overload but
also for immunosuppression, we studied the in vitro effects of
desferrithiocin on T-lymphocyte function. Like deferoxamine,
desferrithiocin inhibited, in a dose-dependent fashion, mitogen- and
lectin-induced proliferation of both human and murine T cells. It was
active at a concentration of 10 micrograms/mL. The inhibition of
proliferation was reversed by ferrous chloride, but not by other metal
salts, recombinant IL-2, or conditioned medium. Desferrithiocin also
inhibited proliferation of constitutively dividing, and factor- independent
EBV-transformed B cell and leukemic T-cell lines. Although desferrithiocin
inhibited the induction of cytotoxic T lymphocyte (CTL) activity, it did
not inhibit CTL- or natural killer-induced cytotoxicity. The agent did not
inhibit the expression of activation antigens such as the IL-2 receptor on
T cells, nor early measures of T- cell activation such as the influx of
intracellular calcium. Thus, desferrithiocin, like deferoxamine, is a
potent and reversible inhibitor of T-cell proliferation. This
anti-proliferative effect inhibits T-cell function. Bioavailability after
oral administration is a unique property of desferrithiocin, and would make
it an attractive alternative to deferoxamine. Its immunomodulating
properties may therefore be exploited in vivo to inhibit graft rejection or
autoreactive T cells.
Volume 76,
Issue 10,
pp. 2052-2059,
11/15/1990
Copyright © 1990 by The American Society of Hematology
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