Proteomic analysis of T cell activation in the presence of cyclosporin A: immunosuppressor and activator removal induces de novo protein synthesis.

Cyclosporin A (CsA), a fungal metabolite used in organ transplantation, blocks the immune responses by interfering with early activation signals preventing the induction of the IL2 gene. We have previously reported that the removal of the immunosuppressor provokes the transcription of the IL2 encoding gene. We have now investigated whether the transcription and translation of other genes accompanies this process. Withdrawal of CsA and Concanavalin A (ConA) from cultures of murine T cells activated by ConA in the presence of CsA leads to substantial changes in the pattern of radio-labelled proteins. A large number of polypeptides were synthesised de novo. In addition, a set of polypeptides detected prior to immunosuppressor elimination was not anymore synthesised. Finally, besides these qualitative changes, quantitative differences in terms of increased or decreased polypeptide abundance were also observed. The results demonstrate that activation in the presence of CsA has programmed the T cells to transcribe and translate a large number of genes, without further reactivation, once the immunosuppressor and the activator were removed.