Editors' ChoiceImmunology

Highlight: IL-2 receptor signaling

See allHide authors and affiliations

Sci. Signal.  19 Dec 2017:
Vol. 10, Issue 510, eaar7668
DOI: 10.1126/scisignal.aar7668

Two papers reveal the consequences of altered interleukin-2 receptor signaling in T lymphocytes.

The cytokine interleukin-2 (IL-2) is important for lymphocyte development, proliferation, and function. IL-2 binds to a receptor complex that includes the IL-2Rβ and IL-2Rγ subunits to activate the transcription factor STAT5 and induce the expression of IL-2–dependent genes. Depending on the lymphocyte subset, it can take hours to days for the effects of IL-2 on cell fate to become apparent.

Two studies in this issue of Science Signaling examined the consequences of IL-2R signaling for different lymphocyte subsets. Smith et al. found that despite having the same IL-2 receptors and intracellular signaling components, CD4+ and CD8+ T cells exhibited different IL-2 signaling dynamics, with CD8+ T cells being more proliferative. Whereas IL-2 stimulated sustained activation of STAT5 in CD8+ T cells, it caused two phases of STAT5 activation in CD4+ T cells. IL-2Rβ was less abundant in CD4+ T cells than in CD8+ T cells and the authors found that CD8+ T cells with reduced IL-2Rβ abundance had a similar pattern of STAT5 activation to that of CD4+ T cells and showed delayed cell cycle entry. These distinct responses may enable an adequate immune response to viruses, which depends on CD8+ T cells, while protecting against autoimmunity caused by overactive CD4+ T cells.

Type 1 diabetes (T1D) is an autoimmune disorder in which CD4+ T cells attack pancreatic β cells. Noting that polymorphisms in the genes encoding IL-2 and its receptor subunits are associated with an increased risk of developing autoimmune diseases, Dwyer et al. expressed a signaling-defective IL-2R variant (IL-2RβY3) in T cells in NOD mice, a model of T1D. Compared with NOD mice expressing the wild-type receptor, those expressing the mutant receptor showed accelerated onset of T1D. Mice expressing IL-2RβY3 in their T cells had reduced numbers and activity of regulatory T cell (Treg) subsets, cells that suppress the activity of effector cells. Furthermore, these mice showed increased infiltration of autoreactive effector T cells in the pancreas. These data suggest that reducing the strength of IL-2 signaling has more of an impact on Tregs than on effector T cells, which may have implications for the therapeutic use of IL-2. Together, both studies highlight how the strength of IL-2 signaling has distinct functional consequences for different lymphocyte subsets.

Highlighted Articles

View Abstract

Navigate This Article