Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology
Source: T cells, mostly CD4 T cells.
Receptor: IL-2 receptor is composed of 3 proteins: IL-2Rα, IL-2Rβ, γc. The receptor engages the Jak3-STAT5 signal transduction pathway. Receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 contain γ chain, which is affected in X-linked
Cytokine receptors (click to enlarge the image).
- T cells: proliferation, increased cytokine synthesis; potentiates Fas-mediated apoptosis; promotes regulatory T cell development, survival
- NK cells: proliferation, activation
- B cells: proliferation, antibody synthesis (in vitro)
Activation of Th2 cells by allergen leads to production of IL-2 and its receptor IL-2Ra.
Binding of IL-2 to Th2 cells expressing IL-2Ra leads to proliferation of that clone of specifically sensitized Th2 cells.
IL-2 promotes proliferation and survival of antigen specific T-cells, hence its old name “T-cell growth factor”.
Humanized mAb approved for prevention of renal allograft rejection that binds to the alpha chain (CD25) of the IL-2 receptor on T cells. Inhibits IL-2–induced proliferation and reduces TH2 and TH1 cytokines from activated T cells. Humanized IL-2Ra or daclizumab (Zenapax) is used for prophylaxis of acute organ rejection in renal transplant patients.
Daclizumab was well tolerated in trials of asthma and was associated with clinical improvment. However, IL-2 has pleiotropic effects and caution is warranted in targeting this key cytokine.
Chimeric IL-2Ra or basiliximab
Chimeric IL-2Ra or basiliximab (Simulect) is used for prophylaxis of acute organ rejection in renal transplant patients.
Recombinant IL-2 (Proleukin)
Recombinant IL-2 (Proleukin) is used in the management of metastatic renal cell carcinoma and metastatic melanoma.
Suited to a T: Interleukin-2 as Therapy for Graft-versus-Host Disease - NEJM, 2011.
Busse, WW, Israel, E, Nelson, HS, et al. Daclizumab improves asthma control in patients with moderate to severe persistent asthma: a randomized, controlled trial. Am J Respir Crit Care Med 2008; 178:1002.
Desensitization protocols may overcome incompatibility barriers in renal transplantation, NEJM, 2011.