ALPHA-BETA AND GAMMA-DELTA T-CELLS CAN SHARE A LATE COMMON PRECURSOR

Background: The subdivision of T cells into alpha beta and gamma delta subtypes is conserved throughout vertebrate development. The respecti ve alpha beta and gamma delta T-cell receptors (TCRs) are encoded by s omatically rearranged genes. There has been broad speculation as to wh ether an individual thymocyte can become either a gamma delta T cell o r an alpha beta T cell as a result of stochastic gene rearrangement pr ocesses, 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 leng th polymorphism (PCR-RFLP) technique, which allows us to examine quant itatively the status of TCR gamma and delta genes in postnatal alpha b eta T cells and their progenitors. Interestingly, such cells are deple ted of productively rearranged delta and gamma genes, which can encode delta and gamma TCR polypeptide chains. However, in mice that can rea rrange TCR delta gene segments, but in which the TCR delta gene is non -functional in other respects, no such depletion of productive rearran gements is seen. Conclusion: The quantitative data that we have obtain ed fulfill the predictions of the stochastic hypothesis: that is, a pr ogenitor T cell first attempts to become a gamma delta T cell and, if unsuccessful, then attempts to become an crp T cell. Thus, alpha beta and gamma delta T cells can derive from a common precursor thymocyte. In the simplest case, therefore, lineage-determining factors are the s uccessful rearrangement of both gamma and delta genes before TCR alpha gene rearrangements occur, which lead to deletion of the TCR delta lo cus and thereby preclude further gamma delta T-cell differentiation. I n contrast, successful rearrangement of the TCR beta locus remains com patible with cells becoming either gamma delta or alpha beta T cells.