Il-7 supports D-J but not V-DJ rearrangement of TCR-beta gene in fetal liver progenitor cells.
The rearrangement of TCR-beta gene, one of the earliest events in T cell development, consists of two consecutive steps: D-J rearrangement and V-DJ rearrangement. The present study examined the signals supporting D-J beta and V-DJ beta rearrangements during early T cell development from progenitor cells that reside in fetal liver. We have found that there is an interval of 1 to 2 days between D-J beta and V-DJ beta rearrangements during the early T cell development from fetal liver progenitor cells in deoxyguanosine-treated thymus lobes. We have also found that IL-7, a cytokine expressed in the subcapsular area of the thymus, can promote D-J beta rearrangement of fetal liver progenitor cells, and that anti-IL-7 and anti-IL-7R Abs inhibit the D-J beta rearrangement and further T cell development of fetal liver progenitor cells in the thymus environment. Interestingly, unlike the thymus environment, IL-7 alone was not capable of supporting V-DJ beta rearrangement in the fetal liver cell cultures. These results indicate that D-J beta rearrangement during fetal liver-derived early T cell development is supported in the thymus by IL-7. Furthermore, the present results demonstrate that IL-7, supporting D-J beta rearrangement, does not promote V-DJ beta rearrangement of fetal liver progenitor cells, suggesting that intrathymic molecules promoting V-DJ beta rearrangement are distinct from IL-7 that supports the D-J beta rearrangement.
Tsuda
S
S
Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Japan.
Rieke
S
S
Hashimoto
Y
Y
Nakauchi
H
H
Takahama
Y
Y
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D003849:Deoxyguanosine / Q000494:pharmacology; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000276:immunology*; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte / Q000187:drug effects / Q000276:immunology*; D015851:Interleukin-7 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D011247:Pregnancy; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism
D015851:Interleukin-7; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003849:Deoxyguanosine