IL-15 and IL-2: A matter of life and death for T cells in vivo

Xian Chang Li, Gulcin Demirci, Sylvie Ferrari-Lacraz, Chris Groves, Anthony Coyle, Thomas R. Malek, Terry B. Strom

Research output: Contribution to journalArticle

259 Scopus citations

Abstract

Interleukin (IL)-2 and IL-15 are redundant in stimulating T-cell proliferation in vitro. Their precise role in viva in governing T-cell expansion and T-cell homeostasis is less clear. Each may have distinct functions and regulate distinct aspects of T-cell activation1-6. The functional receptors for IL-2 and IL-15 consist of a private α-chain, which defines the binding specificity for IL-2 or IL-15, and shared IL-2 receptor β- and γ-chains. The γ-chain is also a critical signaling component of IL-4, IL-7 and IL-9 receptors7. Thus, the γ-chain is called the common γ or γ-c. As these receptor subunits can be expressed individually or in various combinations resulting in the formation of receptors with different affinities, distinct signaling capabilities or both7,8, we hypothesized that differential expression of IL-2 and IL-15 receptor subunits on cycling T cells in viva may direct activated T cells to respond to IL-2 or IL-15, thereby regulating the homeostasis of T-cell response in vivo. By observing in viva T-cell divisions and expression of IL-2 and IL-15 receptor subunits, we demonstrate that IL-15 is a critical growth factor in initiating T cell divisions in vivo, whereas IL-2 limits continued T-cell expansion via downregulation of the γ-c expression. Decreased γ-c expression on cycling T cells reduced sustained Bcl-2 expression and rendered cells susceptible to apoptotic cell death. Our study provides data that IL-2 and IL-15 regulate distinct aspects of primary T-cell expansion in vivo.

Original languageEnglish (US)
Pages (from-to)114-118
Number of pages5
JournalNature medicine
Volume7
Issue number1
DOIs
StatePublished - Feb 5 2001

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Li, X. C., Demirci, G., Ferrari-Lacraz, S., Groves, C., Coyle, A., Malek, T. R., & Strom, T. B. (2001). IL-15 and IL-2: A matter of life and death for T cells in vivo. Nature medicine, 7(1), 114-118. https://doi.org/10.1038/83253