Development of immature thymocytes: initiation of CD3, CD4, and CD8 acquisition parallels down‐regulation of the interleukin 2 receptor α chain

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Abstract
We have previously identified a developmental sequence among immature thymocytes, prior to their expression of the lineage markers CD3, CD4, and CD8. This sequence is marked by transient expression of the interleukin 2 receptor α chain (IL 2Rα). The most mature cells in this sequence (surface phenotype heat‐stable antigen (HSA)++ Pgp‐1− IL 2Rα−) are the immediate precursors to CD4+CD8+ small cortical thymocytes, and have by definition been considered to be CD4−CD8−. We now show that these cells display low levels of surface CD4 and CD8, but not CD3. This low‐level expression begins to appear immediately after the loss of IL 2Rα expression. Northern blot analysis for mRNA expression confirms that these IL 2Rα− cells are transcribing CD4 and CD8 mRNA, in contrast to their immediate (IL 2Rα+) precursor. Upon unstimulated culture, these IL 2Rα− cells gradually acquire high levels of CD4 and CD8, as well as low levels of CD3, whereas IL 2Rα− cells do not. These findings suggest that the IL 2Rα+ subset is the end of the true CD3−CD4−CD8− phase, and that the intracellular signals for CD3, CD4, and CD8 acquisition occur simultaneously with, or immediately prior to, the signal for down‐regulation of IL 2Rα.