Which immunosuppressive agent selectively inhibits IL-2 receptor-mediated activation and causes clearance of activated T cells from the circulation?

Which immunosuppressive agent selectively inhibits IL-2 receptor-mediated activation and causes clearance of activated T cells from the circulation?

• A. Daclizumab
• B. Mycophenolate mofetil
• C. Cyclosporine mofetil
• D. Corticosteroids

Answer: (A)

The concept being tested is blocking IL-2 receptor signaling to stop T cell activation and expansion. IL-2 is a key growth factor for T cells, and its receptor is upregulated on activated T cells (the IL-2 receptor, particularly the alpha chain CD25, is expressed at high levels after activation). By preventing IL-2 from engaging its receptor, T cells cannot receive the signal to proliferate, so activated T cells are not expanded and can be cleared from the circulation. Daclizumab fits this mechanism exactly. It is a monoclonal antibody against CD25, the IL-2 receptor alpha chain, on activated T cells. Binding to CD25 blocks IL-2 from signaling through the receptor, curtailing the growth and survival of those activated T cells and leading to their clearance from the blood. Because resting T cells have low CD25 expression, the effect is relatively selective for activated T cells. In contrast, mycophenolate mofetil inhibits purine synthesis to broadly reduce lymphocyte proliferation, not specifically blocking the IL-2 receptor. Cyclosporine inhibits calcineurin, reducing IL-2 production rather than blocking the receptor itself. Corticosteroids exert wide-ranging anti-inflammatory effects without specifically targeting the IL-2 receptor pathway.

The concept being tested is blocking IL-2 receptor signaling to stop T cell activation and expansion. IL-2 is a key growth factor for T cells, and its receptor is upregulated on activated T cells (the IL-2 receptor, particularly the alpha chain CD25, is expressed at high levels after activation). By preventing IL-2 from engaging its receptor, T cells cannot receive the signal to proliferate, so activated T cells are not expanded and can be cleared from the circulation.

Daclizumab fits this mechanism exactly. It is a monoclonal antibody against CD25, the IL-2 receptor alpha chain, on activated T cells. Binding to CD25 blocks IL-2 from signaling through the receptor, curtailing the growth and survival of those activated T cells and leading to their clearance from the blood. Because resting T cells have low CD25 expression, the effect is relatively selective for activated T cells.

In contrast, mycophenolate mofetil inhibits purine synthesis to broadly reduce lymphocyte proliferation, not specifically blocking the IL-2 receptor. Cyclosporine inhibits calcineurin, reducing IL-2 production rather than blocking the receptor itself. Corticosteroids exert wide-ranging anti-inflammatory effects without specifically targeting the IL-2 receptor pathway.