Delineation of intrathymic T, NK, and dendritic cell (DC) progenitors in fetal and adult rats: demonstration of a bipotent T/DC intermediate precursor.

We previously published study results stating that the early rat fetal liver contains a high frequency of T/dendritic cells (DCs), but rarely T/NK bipotent common progenitors. Now, by using xenogenic rat/SCID mouse fetal thymic organ cultures, we extend these observations to the thymus, in which conflicting data have been published in human and mouse. On the one hand, enriched adult intrathymic CD45+CD2- triple negative for CD8, CD4, and CD3 Ag cell progenitors, which contained both rearranged TCRbeta chain and pre-Talpha chain transcripts, completely lacked NKR-P1A expressing cells, and upon limiting dilution conditions, generated T- and T/DC-containing lobes, but no T/NK or NK ones were found. On the other hand, the CD45+CD2- triple negative for CD8, CD4, and CD3 Ags cell population obtained from 15- and 16-day-old fetal rat thymus can be divided into NKR-P1A- and NKR-P1A(low) cell subpopulations that differ in several aspects. Both cell subsets expressed pre-TCRalpha chain transcripts, but only the former contained fully rearranged TCRbeta chain transcripts. Upon limiting dilution, T cell-committed progenitors were only found in the NKR-P1A- cell population, whereas NK-committed progenitors were present in the NKR-P1A(low) population. More importantly, bipotential T/NK progenitors were very rare and were found only in the NKR-P1A(low) cell population, whereas bipotential T/DC progenitors, only previously suggested in the adult mouse thymus, were observed frequently in the NKR-P1A-CD2- cell subpopulation. Our results demonstrate, therefore, that a common intrathymic T/DC intermediate represents the main T cell developmental pathway in rat thymus.