Effect of cyclosporine on interleukin 2 receptor expression in a human alloreactive T cell clone

The effect of CsA on antigen-induced IL-2 receptor expression was studied on a human T lymphocyte clone (4AS) obtained from cells infiltrating a rejected human kidney. Stimulation of 4AS clone cells with specific antigen (D.BLCL) was strongly inhibited by CsA (50% inhibition of tritiated thymidine uptake at about 12.5 ng/ml). Addition of recombinant IL-2 only partially restored 4AS growth inhibition, suggesting that another antigen-induced activation signal such as IL-2-receptor expression could be impaired by CsA. Using 125I-labeled human recombinant IL-2 and 125I-labeled 33B3.1 (a MoAb directed against TAC antigen), we found that expression of both high and low affinity sites was decreased when clone cells were stimulated with D.BLCL in the presence of CsA and exogenous IL-2 (about 50% inhibition in the presence of 500 ng/ml of CsA). Northern blot analysis of IL-2-receptor m.RNA (TAC antigen m.RNA) showed that inhibition occurred at least in part at the pretranscriptional level.