Interleukin‐2 in the development and control of inflammatory disease

Abstract

Summary: Interleukin-2 (IL-2) has multiple, sometimes opposing, functions during an inflammatory response. It is a potent inducer of T-cell proliferation and T-helper 1 (Th1) and Th2 effector T-cell differentiation and provides T cells with a long-lasting competitive advantage resulting in the optimal survival and function of memory cells. In a regulatory role, IL-2 is important for the development, survival, and function of regulatory T cells, it enhances Fas-mediated activation-induced cell death, and it inhibits the development of inflammatory Th17 cells. Thus, in its dual and contrasting functions, IL-2 contributes to both the induction and the termination of inflammatory immune responses.

Notch controls the magnitude of T helper cell responses by promoting cellular longevity

“…The elevated expression of CD25 in DLL4-Fc stimulated cells could allow stronger IL-2 receptor signaling and activate survival pathways. However, IL-2 can also increase the sensitivity of activated CD4 + T cells to the extrinsic apoptosis pathway (20). Indeed, addition of exogenous IL-2 to control cultures reduced viable CD4 + T-cell numbers (Fig.…”

Evaluation of the Safety and Immunogenicity of Two Antigen Concentrations of the Mtb72F/AS02ACandidate Tuberculosis Vaccine in Purified Protein Derivative-Negative Adults

“…Among these cytokines, IFN-␥ (3, 4, 22, 36) and TNF-␣ (11, 28) seem to be the central effector molecules, leading to autophagy, mycobacterial killing, and macrophage death (12,17,21,29,33). IL-2 is a potent inducer of T-cell proliferation and differentiation and is key to the optimal survival and function of memory cells (20). CD40 ligand has been identified as a marker for activated antigen-specific T cells; it is a costimulatory ligand needed to provide T-cell help (7,13,38).…”

STAT3 Protein Promotes T-cell Survival and Inhibits Interleukin-2 Production through Up-regulation of Class O Forkhead Transcription Factors

“…6 -8 week old CD4-STAT3KO or WT (littermates) mice were immunized by subcutaneous injection of 150 g IRBP and 300 g of human IRBP peptide (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) in 0.2 ml emulsion 1:1 v/v with Complete Freund Adjuvant containing Mycobacterium tuberculosis strain H37RA (2.5 mg/ml). The mice also received Bordetella pertussis toxin (0.2 g/mouse) concurrent with immunization and clinical disease was established by histology as described previously (11).…”

“…2 -2 is one of the hallmarks of TCR signaling and largely responsible for T-cell proliferation and expansion (1). However, transcription of IL-2 is actively suppressed in resting T cells by T-cell quiescence factors (2,3).…”