| First Author | Munitic I | Year | 2004 |
| Journal | Blood | Volume | 104 |
| Issue | 13 | Pages | 4165-72 |
| PubMed ID | 15328149 | Mgi Jnum | J:95271 |
| Mgi Id | MGI:3525768 | Doi | 10.1182/blood-2004-06-2484 |
| Citation | Munitic I, et al. (2004) Dynamic regulation of IL-7 receptor expression is required for normal thymopoiesis. Blood 104(13):4165-72 |
| abstractText | 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. |
