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

被引:248
作者
Li, XC [1 ]
Demirci, G
Ferrari-Lacraz, S
Groves, C
Coyle, A
Malek, TR
Strom, TB
机构
[1] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Div Immunol, Boston, MA 02215 USA
[2] Millennium Pharmaceut Inc, Cambridge, MA USA
[3] Univ Miami, Dept Microbiol & Immunol, Miami, FL 33152 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/83253
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Interleukin (IL)-2 and IL-15 are redundant in stimulating T-cell proliferation in vitro. Their precise role in vivo in governing T-cell expansion and T-cell homeostasis is less clear. Each may have distinct functions and regulate distinct aspects of T-cell activation(1-6). The functional receptors for IL-2 and IL-15 consist of a private ex-chain, which defines the binding specificity for IL-2 or IL-15, and shared IL-2 receptor beta- and gamma -chains. The gamma -chain is also a critical signaling component of IL-4, IL-7 and IL-9 receptors(7). Thus, the gamma -chain is called the common gamma or gamma -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 both(7,8), We hypothesized that differential expression of IL-2 and IL-15 receptor subunits on cycling T cells in vivo 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 vivo 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 gamma -c expression. Decreased gamma -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.
引用
收藏
页码:114 / 118
页数:5
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