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Publication : Beta-selection: abundance of TCRbeta-/gammadelta- CD44- CD25- (DN4) cells in the foetal thymus.

First Author  Hager-Theodorides AL Year  2007
Journal  Eur J Immunol Volume  37
Issue  2 Pages  487-500
PubMed ID  17273993 Mgi Jnum  J:117902
Mgi Id  MGI:3697969 Doi  10.1002/eji.200636503
Citation  Hager-Theodorides AL, et al. (2007) beta-Selection: Abundance of TCRbeta(-)/gammadelta(-) CD44(-)CD25(-) (DN4) cells in the foetal thymus. Eur J Immunol 37(2):487-500
abstractText  Expression of TCRbeta and pre-TCR signalling are essential for differentiation of CD4(-)CD8(-) double negative (DN) thymocytes to the CD4(+)CD8(+) double-positive (DP) stage. Thymocyte development in adult Rag1, Rag2 or TCRbetadelta-deficient mice is arrested at the DN3 stage leading to the assumption that pre-TCR signalling and beta-selection occur at, and are obligatory for, the transition from DN3 to DN4. We show that the majority of DN3 and DN4 cells that differentiate during early embryogenesis in wild-type mice do not express intracellular (ic) TCRbeta/gammadelta. These foetal icTCRbeta(-)/gammadelta(-) DN4 cells were T lineage as determined by expression of Thy1 and icCD3 and TCRbeta DJ rearrangement. In addition, in the foetal Rag1(-/-) thymus, a normal percentage of DN4 cells were present. In wild-type mice after hydrocortisone-induced synchronisation of differentiation, the majority of DN4 cells that first emerged did not express icTCRbeta/gammadelta, showing that adult thymocytes can also differentiate to the DN4 stage independently of pre-TCR signalling. Pre-TCR signalling induced expansion in the DN4 population, but lack of TCRbeta/gammadelta expression did not immediately induce apoptosis. Our data demonstrate in vivo differentiation from DN3 to DN4 cell in the absence of TCRbeta/gammadelta expression in the foetal thymus, and after hydrocortisone treatment of adult mice.
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