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 Malek, Terry B. Strom

Research output: Contribution to journalArticle

255 Citations (Scopus)

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

Fingerprint

Interleukin-15
T-cells
Interleukin-2
T-Lymphocytes
Interleukin-15 Receptors
Interleukin-2 Receptors
Cell Division
Homeostasis
Interleukin-9
Interleukin-7
Cell proliferation
Cell death
Interleukin-4
Intercellular Signaling Peptides and Proteins
Cell Death
Down-Regulation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Li, X. C., Demirci, G., Ferrari-Lacraz, S., Groves, C., Coyle, A., Malek, T., & 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

IL-15 and IL-2 : A matter of life and death for T cells in vivo. / Li, Xian Chang; Demirci, Gulcin; Ferrari-Lacraz, Sylvie; Groves, Chris; Coyle, Anthony; Malek, Thomas; Strom, Terry B.

In: Nature Medicine, Vol. 7, No. 1, 05.02.2001, p. 114-118.

Research output: Contribution to journalArticle

Li, XC, Demirci, G, Ferrari-Lacraz, S, Groves, C, Coyle, A, Malek, T & Strom, TB 2001, 'IL-15 and IL-2: A matter of life and death for T cells in vivo', Nature Medicine, vol. 7, no. 1, pp. 114-118. https://doi.org/10.1038/83253
Li XC, Demirci G, Ferrari-Lacraz S, Groves C, Coyle A, Malek T et al. IL-15 and IL-2: A matter of life and death for T cells in vivo. Nature Medicine. 2001 Feb 5;7(1):114-118. https://doi.org/10.1038/83253
Li, Xian Chang ; Demirci, Gulcin ; Ferrari-Lacraz, Sylvie ; Groves, Chris ; Coyle, Anthony ; Malek, Thomas ; Strom, Terry B. / IL-15 and IL-2 : A matter of life and death for T cells in vivo. In: Nature Medicine. 2001 ; Vol. 7, No. 1. pp. 114-118.
@article{c57db9ac1326471c8e0e51b23ef3b1c0,
title = "IL-15 and IL-2: A matter of life and death for T cells in vivo",
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.",
author = "Li, {Xian Chang} and Gulcin Demirci and Sylvie Ferrari-Lacraz and Chris Groves and Anthony Coyle and Thomas Malek and Strom, {Terry B.}",
year = "2001",
month = "2",
day = "5",
doi = "10.1038/83253",
language = "English",
volume = "7",
pages = "114--118",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - IL-15 and IL-2

T2 - A matter of life and death for T cells in vivo

AU - Li, Xian Chang

AU - Demirci, Gulcin

AU - Ferrari-Lacraz, Sylvie

AU - Groves, Chris

AU - Coyle, Anthony

AU - Malek, Thomas

AU - Strom, Terry B.

PY - 2001/2/5

Y1 - 2001/2/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0035132135&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035132135&partnerID=8YFLogxK

U2 - 10.1038/83253

DO - 10.1038/83253

M3 - Article

C2 - 11135625

AN - SCOPUS:0035132135

VL - 7

SP - 114

EP - 118

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 1

ER -