Kinetics of T cell receptor β, γ, and δ rearrangements during adult thymic development:: T cell receptor rearrangements are present in CD44+CD25+ Pro-T thymocytes

We performed a comprehensive analysis of T cell receptor (TCR) gamma rearrangements in T cell precursors of the mouse adult thymus. Using a sensitive quantitative PCR method, we show that TCR gamma rearrangements are present in CD44(+)CD25(+) Pro-T thymocytes much earlier than expected. TCR gamma rearrangements increase significantly from the Pro-T to the CD44(-)CD25(+) Pre-T cell transition, and follow different patterns depending on each V gamma gene segment, suggesting that ordered waves of TCR gamma rearrangement exist in the adult mouse thymus as has been described in the fetal mouse thymus. Recombinations of TCR gamma genes occur concurrently with TCR delta and D-JP rearrangements, but before VP gene assembly. productive TCR gamma rearrangements do not increase significantly before the Pre-T cell stage and are depleted in CD4(+)CD8(+) double-positive cells from normal mice. In contrast, double-positive thymocytes from TCR delta-/- mice display random proportions of TCR gamma rearranged alleles, supporting a role for functional TCR gamma/delta rearrangements in the y delta divergence process.