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

Autori
Munitić, Ivana ; Williams, J.A. ; Yang, Y. ; Dong, B. ; Lucas, P.J. ; El Kassar, N. ; Gress, R.E. ; Ashwell, J.D.

Izvornik
Blood (0006-4971) 104 (2004), 13; 4165-4172

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
IL-7, thymopoiesis, IL-7R, thymic selection

Sažetak
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 α chain (IL-7Rα) transgenic (Tg) mice in which IL-7R is expressed throughout ontogeny. There was no effect of the IL-7Rα Tg on negative selection. Surprisingly, however, although the thymi of IL-7Rα 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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA