Interleukin-2 at the Crossroads of Effector Responses, Tolerance, and Immunotherapy

By W. Liao, Jian-Xin Lin, W. Leonard. Immunity, 2013

1,030 citations recorded by the source corpus.

Interleukin-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 NK 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 (Treg) 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.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/27771a466404b0157626186f2d9655a47fd2c7b6

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Citations in the corpus

• Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells. (2016, background): “Although IL2 promotes effector differentiation and glycolysis in CD8+ T cells (Finlay et al., 2012; Liao et al., 2013; Pipkin et al., 2010), IL7 and IL15 have been implicated in the maintenance of memory T cells and increased mitochondrial biogenesis (Ku et al., 2000; Schluns and Lefrançois, 2003;…”
• IL-2 modulates the TCR signaling threshold for CD8 but not CD4 T cell proliferation on a single cell level (2017, background): “Higher doses of IL-2 (.500 U/ml) stimulate the intermediate affinity IL-2 receptor complex of IL-2Rb (CD122) and IL-2Rg (CD132) (21), which we observed when stimulating naive CD8 OTI T cells with IL-2 doses over 300 U/ml.”
• Immunological Synapse Predicts Effectiveness of Chimeric Antigen Receptor Cells (2018, background): “Moreover, interleukin-2 (IL-2) expression is a significant biomarker for efficient T cell activation.(29,30) Thus, intracellular IL-2 staining was also examined.”
• The Balance of Th17 versus Treg Cells in Autoimmunity (2018, background): “However, TGF-β inhibits differentiation of Th1 and Th2 cells, and IL-2 inhibits that of Th17 cells [66,67].”