α β and γ δ T cells can share a late common precursor

AbstractBackground: The subdivision of T cells into αβ and γδ subtypes is conserved throughout vertebrate development. The respective αβ and γδ T-cell receptors (TCRs) are encoded by somatically rearranged genes. There has been broad speculation as to whether an individual thymocyte can become either a γδ T cell or an αβ T cell as a result of stochastic gene rearrangement processes, or whether the two types of T cell are derived from separate lineages. Many of the experimental findings are apparently conflicting, however, and the issue — a basic one in immunology and development — remains unresolved.Results To address this issue, we have used the recently developed polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) technique, which allows us to examine quantitatively the status of TCR γ and δ genes in postnatal αβ T cells and their progenitors. Interestingly, such cells are depleted of productively rearranged δ and γ genes, which can encode δ and γ TCR polypeptide chains. However, in mice that can rearrange TCRδ gene segments, but in which the TCRδ gene is non-functional in other respects, no such depletion of productive rearrangements is seen.Conclusion The quantitative data that we have obtained fulfill the predictions of the stochastic hypothesis: that is, a progenitor T cell first attempts to become a γδ T cell and, if unsuccessful, then attempts to become an αβ T cell. Thus, αβ and γδ T cells can derive from a common precursor thymocyte. In the simplest case, therefore, lineage-determining factors are the successful rearrangement of both γ and δ genes before TCRα gene rearrangements occur, which lead to deletion of the TCRδ locus and thereby preclude further γδ T-cell differentiation. In contrast, successful rearrangement of the TCRβ locus remains compatible with cells becoming either γδ or αβ T cells