Which topical immunosuppressant primarily functions by inhibiting T cell activation by inhibiting IL-2?

Which topical immunosuppressant primarily functions by inhibiting T cell activation by inhibiting IL-2?

• A. Tacrolimus
• B. Cyclosporine
• C. Sirolimus
• D. Everolimus

Answer: (B)

Blocking IL-2 production stops T cell activation. The key step is the calcineurin–NFAT pathway: when calcineurin is active, NFAT is dephosphorylated and moves into the nucleus to drive IL-2 gene transcription. Cyclosporine binds cyclophilin, and this complex inhibits calcineurin. With calcineurin inhibited, NFAT cannot activate IL-2 transcription, so T cells don’t get the IL-2 signal needed for activation and clonal expansion. Sirolimus and everolimus act later in the pathway by blocking mTOR, which prevents T cell proliferation in response to IL-2 rather than reducing IL-2 production itself. Tacrolimus also inhibits calcineurin via FKBP-12, producing the same reduction in IL-2, but the classic mechanism described for this blocking of IL-2 production is cyclosporine’s action.

Blocking IL-2 production stops T cell activation. The key step is the calcineurin–NFAT pathway: when calcineurin is active, NFAT is dephosphorylated and moves into the nucleus to drive IL-2 gene transcription. Cyclosporine binds cyclophilin, and this complex inhibits calcineurin. With calcineurin inhibited, NFAT cannot activate IL-2 transcription, so T cells don’t get the IL-2 signal needed for activation and clonal expansion.

Sirolimus and everolimus act later in the pathway by blocking mTOR, which prevents T cell proliferation in response to IL-2 rather than reducing IL-2 production itself. Tacrolimus also inhibits calcineurin via FKBP-12, producing the same reduction in IL-2, but the classic mechanism described for this blocking of IL-2 production is cyclosporine’s action.