DIRECT ANTI-PROLIFERATIVE EFFECTS OF CYCLOSPORIN-A ON MURINE LYMPHORETICULAR TUMOR-CELLS IN CULTURE

  • 1 January 1983
    • journal article
    • research article
    • Vol. 2  (2) , 121-132
Abstract
Cyclosporin A (CSA) prevents mouse spleen cell blast formation in response to concanavalin A (Con A) and inhibits lymphocyte proliferation. In the presence of interleukin-2 (Il-2), the proliferation of preformed blasts is not affected by CSA. The effects of CSA were studied on the growth in culture of several established mouse lymphoreticular tumor cell lines proliferating independently of exogenous lymphokines. CSA abolished, by direct cytolysis, growth of the T lymphoma lines, EL4, WEHI22.1, S49.1, RL .male. 1, WR19L and YAC. Growth of the non-T cell lines, S49, P388D1 [leukemia] RAW264.7, PU51.R, P815 [mastocytoma], P3X63Ag8 [myeloma] and L929 [fibrosarcoma], was variably retarded by a noncytocidal action of CSA. The concentration of CSA required for T cell cytolysis was relatively high and directly related to the numbers of cells treated. Expression of Thy-1 antigen predicted for the susceptibility of a cell line to CSA-induced lysis. At the concentrations used there was no evidence of significant mitotic death following CSA treatment; cells previously exposed to CSA and then washed were able to resume a delayed but otherwise normal pattern of replication. In a preliminary experiment, CSA afforded significant protection to C57BL/6 mice transplanted with syngeneic EL4 cells. CSA, in vitro and in vivo, is a potent antiproliferative agent selective for T cells, and in the absence of growth factors its inhibitory effects are not limited to early event(s) in the T cell activation process.