Ontogeny of fetal CD8^lo4^lo thymocytes: Expression of CD44, CD25 and early expression of TcR α mRNA

CD8^lo 4^lo cells are the immediate precursors of immature CD8^hi4^lcTcR^lo, CD8^hi 4^hiTcR^lo and CD8^hi4^hiTcR^lo double‐positive (DP) thymocytes in the adult murine thymus. These cells are the first subset in the adult thymus to express accessory CD8 and CD4 molecules, to rearrange the T cell receptor (TcR) a chain genes and to express the TcR αβ heterodimer at low levels at the surface. Here, we investigate the fetal ontogeny of CD8^lo 4^lo cells. We detect these cells on day 15 of fetal development. They dominate the thymus on day 15.5, to become progressively less prominent thereafter. An important characteristic of fetal CD8^lo 4^lo cells is the early expression of TcR α mRNA (on fetal day 15, 36–48 h earlier than reported previously). Our results also suggest, but do not prove, that the receptor may be expressed on the surface as early as day 15.5. Fetal CD8^lo 4^lo cells, like their adult counterparts, become DP in vitro. However, early fetal CD8^lo 4^lo thymocytes express both CD44 and CD25 – unlike the adult subset ‐ and that links them to their putative precursors, fetal CD44⁺CD25⁺ double‐negative cells. This finding underscores the difference between adult and fetal thymocytes in turnover of membrane molecules and/or the kinetics of progression through phenotypic stages.