Extensive proliferation of T cell lineage-restricted progenitors in the thymus: an essential process for clonal expression of diverse T cell receptor beta chains

For clonal diversification of TCR, a large number of T cell progenitors are required in which highly diverse TCRbeta chains are accommodated individually. In the present study, we examined the proliferative potential of thymic progenitors that have been defined to be T cell lineage restricted. We show that the earliest fetal thymus (FT) cells from Rag2(-/-) mice, when cultured individually in a thymic organ culture system, produced 150-1,800 CD25(+) cells. Since differentiation and proliferation of Rag2(-/-) thymocytes are arrested at the stage of TCRbeta chain gene rearrangement, the observed proliferation was considered to represent the proliferative potential of progenitors prior to the TCRbeta rearrangement. A comparable level of proliferation was revealed to occur by analyzing the Dbeta-Jbeta rearrangement profiles of T cells generated from single progenitors in the earliest population of FT from normal mice. The proliferative potential of progenitors declined along with the progression of developmental stages. Such an extensive proliferation of progenitors after the restriction to the T cell lineage may be an essential process ensuring the clonal diversification of TCRbeta chains.