Dynamic regulation of IL-7 receptor expression is required for normal thymopoiesis.
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.
Munitic
Ivana
I
Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Williams
Joy A
JA
Yang
Yili
Y
Dong
Bei
B
Lucas
Philip J
PJ
El Kassar
Nahed
N
Gress
Ronald E
RE
Ashwell
Jonathan D
JD
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology; D020287:In Situ Nick-End Labeling; D015851:Interleukin-7 / Q000276:immunology; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020395:Receptors, Interleukin-7 / Q000235:genetics* / Q000276:immunology*; D012641:Selection, Genetic; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D018076:DNA, Complementary; D015851:Interleukin-7; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain