Autocrine growth of a human T-cell line is inhibited by cyclosporin A
A Dautry-Varsat, A Hemar, V Cornet and V Duprez
Unite de Genetique Somatique (UA CNRS 361), Institut Pasteur, Paris,
France.
The effect of cyclosporin A (CsA), a potent immunosuppressive agent, on a
human T-cell line, IARC 301, which constitutively secretes interleukin-2
(IL-2) and expresses high-affinity IL-2 receptors, was investigated. We
show that CsA inhibits IARC 301 cell growth. CsA also prevents the
constitutive secretion of IL-2 in this T-cell line by blocking
transcription of the IL-2 gene. If exogenous IL-2 is added together with
CsA for 3 days, the cells grow as well as untreated controls. Thus, under
such conditions, CsA inhibits IARC 301 growth by preventing its endogenous
constitutive IL-2 synthesis. This demonstrates that IL-2 stimulates the
proliferation of this cell line by an autocrine pathway, in agreement with
our previous data. We also show for the first time, that CsA not only can
inhibit IL-2 production of T cells upon activation, but that it can also
prevent ongoing constitutive IL-2 synthesis of a T-cell line. Autocrine
growth stimulation of tumor cells by cytokines has been demonstrated in a
few cases. CsA inhibits synthesis of several cytokines. Probing for the
autocrine growth of tumor cells by studying the effect of CsA and its
reversibility by cytokines on their proliferation may be simple and useful.
Volume 72,
Issue 2,
pp. 588-592,
08/01/1988
Copyright © 1988 by The American Society of Hematology
