Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy.
Interleukin-2 (IL-2) is a pleiotropic cytokine produced after antigen activation that plays pivotal roles in the immune response. Discovered as a T cell growth factor, IL-2 additionally promotes CD8(+) T cell and natural killer cell cytolytic activity and modulates T cell differentiation programs in response to antigen, promoting naïve CD4(+) T cell differentiation into T helper 1 (Th1) and T helper 2 (Th2) cells while inhibiting T helper 17 (Th17) and T follicular helper (Tfh) cell differentiation. Moreover, IL-2 is essential for the development and maintenance of T regulatory cells and for activation-induced cell death, thereby mediating tolerance and limiting inappropriate immune reactions. In this review, we focus on the molecular mechanisms and complex cellular actions of IL-2, its cooperative and opposing effects with other cytokines, and how both promoting and blocking the actions of IL-2 are being utilized in clinical medicine.
Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1674, USA.
Wei
W
Liao
Jian-Xin
JX
Lin
Warren J
WJ
Leonard
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007156:Immunologic Memory; D007167:Immunotherapy; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism / Q000502:physiology*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000276:immunology / Q000628:therapy; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D053632:X-Linked Combined Immunodeficiency Diseases / Q000235:genetics / Q000276:immunology / Q000628:therapy
D053631:Interleukin Receptor Common gamma Subunit; D019409:Interleukin-15; D007376:Interleukin-2; D015375:Receptors, Interleukin-2