Cyclosporin A inhibits interleukin 2-dependent growth of alloactivated cloned human T-lymphocytes.
The effect of cyclosporin A (CsA) on the growth of mixed leukocyte culture-derived human cloned T-cells with different functions has been studied. Interleukin 2-dependent clones with allospecific cytotoxic, natural killer-like cytotoxic, lymphoproliferation suppressive, or primed lymphocyte typing function, were used as test cells in short term (36 h) tritiated thymidine incorporation assays. CsA inhibited growth of these cells in a dose-dependent manner, and the lowest concentration of CsA tested (0.1 microgram/ml) was already inhibitory for the majority of clones. Differences between clones in their susceptibility to CsA as measured in this assay did not correlate with their defined functions. Long term (2-3 week) growth of cloned cells cultured in the presence of CsA was also depressed in a dose-dependent manner; moreover, in the case of a suppressor cell clone, as well as a natural killer-like cytotoxic, and a primed lymphocyte typing clone, function of cells surviving after preculture with CsA was suppressed too. It may be important that NK-like effector function and growth of an NK-like T-cell clone showed more resistance to the inhibitory action of CsA than a PLT clone. These data show that previously alloactivated continuously proliferating Interleukin 2-dependent human T-cell clones are fully susceptible to CsA-mediated inhibition of their function as well as their proliferation. Thus, CsA can exert a strong immunosuppressive effect not only by preventing initial activation of T-cells.
D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D003524:Cyclosporins / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
D003524:Cyclosporins; D007376:Interleukin-2; D004247:DNA