Calcineurin inhibitors (tacrolimus and cyclosporine) used in solid organ transplant immunosuppression inhibit which specific molecular pathway?
- A Inhibit calcineurin phosphatase, preventing dephosphorylation of NFAT, thereby blocking IL-2 gene transcription ✓
- B Block mTOR complex, inhibiting T-cell proliferation in response to IL-2 signalling
- C Block CD80/CD86–CD28 co-stimulatory signalling, preventing T-cell activation
- D Inhibit DNA synthesis by blocking purine nucleotide production in activated T-cells
Correct answer: A. Inhibit calcineurin phosphatase, preventing dephosphorylation of NFAT, thereby blocking IL-2 gene transcription
Explanation
Calcineurin inhibitors (tacrolimus via FKBP12 complex, cyclosporine via cyclophilin complex) inhibit the phosphatase activity of calcineurin. This prevents dephosphorylation and nuclear translocation of NFAT (nuclear factor of activated T-cells), thereby blocking transcription of IL-2 and other cytokines essential for T-cell activation and clonal expansion. mTOR inhibitors (sirolimus, everolimus) block the mTOR pathway (option B). Belatacept blocks CD80/CD86–CD28 co-stimulation (option C). Azathioprine/mycophenolate inhibit purine synthesis (option D).
Reference: Bailey & Love's Short Practice of Surgery, 27th ed.
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