Dynamic regulation of IL-7 receptor expression is required for normal thymopoiesis

被引:82
作者
Munitic, I
Williams, JA
Yang, YL
Bei, D
Lucas, PJ
El Kassar, N
Gress, RE
Ashwell, JD
机构
[1] NCI, Lab Immune Cell Biol, Natl Inst Hlth, Bethesda, MD 20892 USA
[2] US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Rockville, MD 20857 USA
[3] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA
关键词
D O I
10.1182/blood-2004-06-2484
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Interleukin-7 receptor (IL-7R) levels are tightly controlled during ontogeny: high on double-negative (DN) cells, absent on double-positive (DP) cells, and high once again on thymocytes undergoing positive selection. To determine if loss of IL-7-mediated survival signals in DP cells is necessary for normal antigen-specific selection, we created T-lineage-specific lL-7R alpha chain (IL-7Ralpha) transgenic (Tg) mice in which IL-7R is expressed throughout ontogeny. There was no effect of the IL-7Ralpha Tg on negative selection. Surprisingly, however, although the thymi of IL-7Ralpha Tg mice were comparable at birth, there was a decrease in thymocyte number as the mice aged. This was found to be due to competition between DN and IL-7R-expressing DP cells for endogenous IL-7, which resulted in decreased levels of Bcl-2 in DIN cells, increased DIN apoptosis, and decreased DN cell number. Therefore, the down-regulation of IL-7R on DP cells is an "altruistic" act required for maintaining an adequate supply of local IL-7 for DN cells. (C) 2004 by The American Society of Hematology.
引用
收藏
页码:4165 / 4172
页数:8
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