Which immunosuppressive drug inhibits calcineurin, reducing IL-2 production and T cell activation?

• A. Prednisone
• B. Methotrexate
• C. Tacrolimus
• D. Azathioprine

Answer: (C)

Calcineurin inhibitors suppress T cell activation by blocking the dephosphorylation of NFAT, a step required for NFAT to enter the nucleus and drive IL-2 gene transcription. Without IL-2, T cell proliferation is markedly reduced. Tacrolimus binds the intracellular protein FKBP12, and this complex inhibits calcineurin’s phosphatase activity, preventing NFAT activation and IL-2 production. This direct interference with the calcineurin–NFAT–IL-2 axis is what makes tacrolimus effective at dampening T cell–mediated immune responses. Other immunosuppressants work by different routes—glucocorticoids like prednisone broadly suppress inflammatory gene transcription; methotrexate and azathioprine impede nucleotide synthesis and lymphocyte proliferation—so they don’t specifically target calcineurin or IL-2 production.