Journal
JOURNAL OF IMMUNOLOGY
Volume 184, Issue 12, Pages 6670-6679Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0901508
Keywords
-
Categories
Funding
- Landsteiner Foundation for Blood Transfusion Research
- Dutch Cancer Society
- Netherlands Organization for Scientific Research-Aard-en Levenswetenschappen
Ask authors/readers for more resources
The cytokine IL-15 and the inhibitor of DNA binding (Id) 2, which negatively regulates the activity of basic helix-loop-helix transcription factors, have been shown to play key roles in NK cell development. Consistent with this, exogenous IL-15 added to human thymic progenitor cells stimulated their development into NK cells at the expense of T cells both in fetal thymic organ culture and in coculture with stromal cells expressing the Notch ligand Delta-like 1. Overexpression of Id2 in thymic progenitor cells stimulated NK cell development and blocked T cell development. This, in part, is attributed to inhibition of the transcriptional activity of the E protein HEB, which we show in this study is the only E protein that enhanced T cell development. Notably, Id2 increased a pool of lineage CD1a(-)CD5(+) progenitor cells that in synergy with IL-15 furthered expansion and differentiation into NK cells. Taken together, our findings point to a dualistic function of Id2 in controlling T/NK cell lineage decisions; T cell development is impaired by Id2, most likely by sequestering HEB, whereas NK cell development is promoted by increasing a pool of CD1a(-)CD5(+) NK cell progenitors, which together with IL-15 differentiate into mature NK cells. The Journal of Immunology, 2010, 184: 6670-6679.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available