Growth, interleukin-2 production, and responsiveness to IL-2 in T4-
positive T Lymphocyte populations from malignant cutaneous T cell lymphoma
(Sezary's syndrome): the effect of cyclosporin A
W Solbach, CE Lange, M Rollinghoff and H Wagner
Functional analysis and surface phenotyping using monoclonal antibodies
have revealed that malignant T lymphocyte populations in the peripheral
blood of patients with Sezary's syndrome resemble the T helper cell
populations from normal individuals. In this article we have studied the
effects of the immunosuppressive drug cyclosporine A (CsA) on growth,
interleukin-2 (IL-2) production, and the induction of IL-2 responsiveness
of peripheral blood monocytes (PBMs) from five patients with Sezary's
syndrome in vitro, using the lectin phytohemagglutinin (PHA) and the
phorbol ester phorbol myristate acetate (PMA) as stimuli. The following
results were obtained: PHA-induced cell proliferation was significantly
more sensitive to inhibition by CsA than that induced by PMA or a
combination of PMA and PHA (P less than .005). Sezary PBMs produced only
small amounts of IL-2 in response to PHA. Stimulation with PMA, however,
resulted in significant IL-2 production. PMA and PHA, when given in
combination, acted synergistically. The low levels of IL-2 production
induced by PHA or PMA were more sensitive to CsA- mediated suppression than
those induced by a combination of PHA and PMA (75% and 55% suppression,
respectively). CsA-mediated growth suppression could be overcome if the
cultures were supplemented with appropriate amounts of exogenous IL-2. We
conclude from our data, that CsA in Sezary PBMs inhibits T cell growth
indirectly as a consequence of suppression of IL-2 growth indirectly as a
consequence of suppression of IL-2 production. Moreover, like normal T
lymphocytes, Sezary PBMs do not express the IL-2 receptor spontaneously,
but can be induced to do so. CsA does not interfere with intracellular
events leading to the expression and the biologic function of the IL-2
receptor.
Volume 64,
Issue 5,
pp. 1022-1027,
11/01/1984
Copyright © 1984 by The American Society of Hematology
