T Cell Lineage Determination Precedes the Initiation of Tcr Gene Rearrangement

Masuda, K.; Kakugawa, K.; Nakayama, T.; Minato, N.; Katsura, Y.; Kawamoto, H.

The Journal of Immunology 179(6): 3699-3706

2007


DOI: 10.4049/jimmunol.179.6.3699
Accession: 068490772

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Abstract
Loss of dendritic cell potential is one of the major events in intrathymic T cell development, during which the progenitors become determined to the T cell lineage. However, it remains unclear whether this event occurs in synchrony with another important event, TCRbeta chain gene rearrangement, which has been considered the definitive sign of irreversible T cell lineage commitment. To address this issue, we used transgenic mice in which GFP expression is controlled by the lck proximal promoter. We found that the double-negative (DN) 2 stage can be subdivided into GFP- and GFP+ populations, representing functionally different developmental stages in that the GFP-DN2, but not GFP+DN2, cells retain dendritic cell potential. The GFP+DN2 cells were found to undergo several rounds of proliferation before the initiation of TCRbeta rearrangement as evidenced by the diversity of D-Jbeta rearrangements seen in T cells derived from a single GFP+DN2 progenitor. These results indicated that the determination step of progenitors to the T cell lineage is a separable event from TCRbeta rearrangement.