Effects of interleukin-2 in immunostimulation and immunosuppression

Abstract

Historically, interleukin-2 (IL-2) was first described as an immunostimulatory factor that supports the expansion of activated effector T cells. A layer of sophistication arose when regulatory CD4+ T lymphocytes (Tregs) were shown to require IL-2 for their development, homeostasis, and immunosuppressive functions. Fundamental distinctions in the nature and spatiotemporal expression patterns of IL-2 receptor subunits on naive/memory/effector T cells versus Tregs are now being exploited to manipulate the immunomodulatory effects of IL-2 for therapeutic purposes. Although high-dose IL-2 administration has yielded discrete clinical responses, low-dose IL-2 as well as innovative strategies based on IL-2 derivatives, including “muteins,” immunocomplexes, and immunocytokines, are being explored to therapeutically enhance or inhibit the immune response.

Diagnostic and Immunotherapeutic Value of CD248 in Renal Cell Carcinoma

“…Additionally, CD8 + cytotoxic T lymphocytes (CTLs) were positively correlated with the risk score, however, increased CTLs resulted in RCC metastasis instead of killing effect. Thus, we speculate CTLs-mediated anti-tumor response is counterbalanced by strong immunosuppression of Tregs, which consequentially facilitate the survival of cancer cells [31,32].…”

Correlation study between blood cytokines and lymphocytes in early postoperative critical patients with compromised immune function

“…IL-2 could orchestrate the differentiation of T helper (T h ) 1 cells and the production of type 1 cytokines like interferon-gamma (IFN-γ). [ 13 – 17 ] IL-2 is also shown to be able to activate macrophages, induce the differentiation of various killer cells (cytotoxic T cells and natural killer [NK] cells), and enhance the ability of the body to clear infection. [ 18 ] Recombinant human IL-2 protein has been approved for the treatment of kidney cancer and melanoma as early as 1992 and 1998, respectively.…”

Antigen presentation, autoantibody production, and therapeutic targets in autoimmune liver disease

“…In addition, supplementation with vitamins such as all-trans-retinoic acid and vitamin D have been used to promote Treg expansion. 5,[248][249][250][251][252][253][254] In addition, gene editing of Tregs has become an additional strategy for optimizing Tregbased therapies. Peripheral Tregs express CXCR3, which greatly enhances the hepatic recruitment of Tregs by intrahepatic synthesis of the cognate ligands CXCL9-11.…”