Munitic Ivana, Williams Joy A, Yang Yili, Dong Bei, Lucas Philip J, El Kassar Nahed, Gress Ronald E, Ashwell Jonathan D
Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Blood. 2004 Dec 15;104(13):4165-72. doi: 10.1182/blood-2004-06-2484. Epub 2004 Aug 24.
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 IL-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 DN cells, increased DN 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.
在个体发育过程中，白细胞介素-7受体（IL-7R）水平受到严格调控：在双阴性（DN）细胞上水平较高，在双阳性（DP）细胞上缺失，而在经历阳性选择的胸腺细胞上再次升高。为了确定DP细胞中IL-7介导的生存信号缺失对于正常抗原特异性选择是否必要，我们构建了T细胞谱系特异性IL-7Rα链（IL-7Rα）转基因（Tg）小鼠，其中IL-7R在整个个体发育过程中均有表达。IL-7Rα Tg对阴性选择没有影响。然而，令人惊讶的是，尽管IL-7Rα Tg小鼠的胸腺在出生时相当，但随着小鼠年龄增长，胸腺细胞数量减少。发现这是由于DN细胞与表达IL-7R的DP细胞对内源性IL-7的竞争，导致DN细胞中Bcl-2水平降低，DN细胞凋亡增加，DN细胞数量减少。因此，DP细胞上IL-7R的下调是为DN细胞维持足够局部IL-7供应所需的一种“利他”行为。
