PMID- 15328149 OWN - NLM STAT- MEDLINE DCOM- 20050324 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 104 IP - 13 DP - 2004 Dec 15 TI - Dynamic regulation of IL-7 receptor expression is required for normal thymopoiesis. PG - 4165-72 AB - 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. FAU - Munitic, Ivana AU - Munitic I AD - Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Williams, Joy A AU - Williams JA FAU - Yang, Yili AU - Yang Y FAU - Dong, Bei AU - Dong B FAU - Lucas, Philip J AU - Lucas PJ FAU - El Kassar, Nahed AU - El Kassar N FAU - Gress, Ronald E AU - Gress RE FAU - Ashwell, Jonathan D AU - Ashwell JD LA - eng PT - Journal Article DEP - 20040824 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (DNA, Complementary) RN - 0 (Interleukin-7) RN - 0 (Receptors, Interleukin-7) RN - 0 (interleukin-7 receptor, alpha chain) SB - IM MH - Animals MH - Apoptosis/immunology MH - DNA, Complementary/genetics MH - Gene Expression Regulation/immunology MH - In Situ Nick-End Labeling MH - Interleukin-7/immunology MH - Lymphopoiesis/genetics/*immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Receptors, Interleukin-7/*genetics/*immunology MH - Selection, Genetic MH - T-Lymphocytes/*immunology MH - Thymus Gland/immunology EDAT- 2004/08/26 05:00 MHDA- 2005/03/25 09:00 CRDT- 2004/08/26 05:00 PHST- 2004/08/26 05:00 [pubmed] PHST- 2005/03/25 09:00 [medline] PHST- 2004/08/26 05:00 [entrez] AID - S0006-4971(20)49062-7 [pii] AID - 10.1182/blood-2004-06-2484 [doi] PST - ppublish SO - Blood. 2004 Dec 15;104(13):4165-72. doi: 10.1182/blood-2004-06-2484. Epub 2004 Aug 24.