Intrathymic a T-cell development proceeds via an ordered sequence of phenotypic changes. CD48 TCR triple-negative (TN) precursors develop into mature TCRM CD48 or CD4 8 single-positive (SP) cells via the immature CD84 double-positive (DP) intermediate. Within the TN compartment, CD44 and CD25 were used to delineate four sequential stages: CD44'25-"442544 25-'44"25. In parallel to this main DN-DPSP pathway, a numerically minor pathway (DN<>mDN) gives rise lo mature DN (mDN) cells, which are TCR"" . To assess the role of TCR in the commitment to either the major or minor pathway, we prepared chimeric mice by injecting a 1:1 mixture of two TCR-transgenic mice (TCRTg) bone marrows into lethaily irradiated B6/Ly5.2 mice. Three TCRTg were used: H-Y. 2C, and OT-1, specific for male antigen, LJ. and OVA"7 '" peptide, respectively. When two TCRTg populations developed in the thymus, one consistently predominated (in a ratio 7-9:1) at the DP and SP stages following the hierarchy: nonTg>OT-l>H-Y>2C. Surprisingly, at the DN stage the expression of both TCRTg was similar. Tracing early thymocyte development using congenic markers, we showed that the "selection" of one TCR to the major pathway occurs at or after CD8 4 CD25 stage. For this reason, we analyzed the DN compartment in the TCRTg mice. In all three strains, there is an accumulation (80%) of CD44CD25 NK1.1 CD38 cells. The expression of preTa and RAG together with the impaired conversion of CD4425'CD8 4'° into DP cells correlated with the ability of TCRTg cells to expand in mixed chimeras. Possible reasons for the block in DNDP conversion are discussed.
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology