Induction of TCR gene rearrangements in uncommitted stem cells by a subset of IL-7 producing, MHC class-II-expressing thymic stromal cells.
The embryonic thymic microenvironment provides the necessary elements for T cell lineage commitment, but the precise role of individual stromal cell components remains to be determined. Here we address the question of which stromal cell types are required for initiation of V-DJ rearrangements of the TCR-beta and TCR-delta locus in CD117+CD45+ uncommitted fetal liver progenitors. We show that fetal thymic stroma alone is necessary and sufficient for induction of TCR-beta and TCR-delta rearrangements. Furthermore, the ability to induce this T cell commitment step is confined to a subset of MHC class II-positive epithelial cells. Thymic stroma derived from mice with a targeted deletion in the IL-7 gene, however, lacks this ability. These findings set the stage for a further definition of the nature of the thymic stromal cell support in the regulation of T cell commitment.
Oosterwegel
M A
MA
Division of Immunology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam.
Haks
M C
MC
Jeffry
U
U
Murray
R
R
Kruisbeek
A M
AM
D000818:Animals; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D005333:Fetus; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology*; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D015851:Interleukin-7 / Q000096:biosynthesis*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*
D000949:Histocompatibility Antigens Class II; D015851:Interleukin-7