Research ArticleImmunology

IL-2Rβ abundance differentially tunes IL-2 signaling dynamics in CD4+ and CD8+ T cells

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Science Signaling  19 Dec 2017:
Vol. 10, Issue 510, eaan4931
DOI: 10.1126/scisignal.aan4931

Receptor abundance defines signaling dynamics

Although the cytokine interleukin-2 (IL-2) stimulates the same receptors and intracellular signaling components in CD4+ and CD8+ T cells, these cells exhibit different responses to IL-2. Both cell types proliferate in response to IL-2, but CD8+ T cells enter the S phase earlier and are more proliferative than CD4+ T cells. Smith et al. found that whereas IL-2 stimulated sustained phosphorylation of the transcription factor STAT5 in CD8+ T cells, it caused CD4+ T cells to exhibit two phases of STAT5 phosphorylation. The IL-2 receptor subunit IL-2Rβ was less abundant in CD4+ T cells than in CD8+ T cells. Reducing IL-2Rβ in CD8+ T cells made these cells exhibit a CD4+ T cell–like pattern of STAT5 phosphorylation and delayed cell cycle entry. These distinct IL-2 signaling dynamics may tune the responses of CD4+ and CD8+ T cells to enable an adequate immune response while protecting against autoimmunity.

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