TCR Expression in Human Fetal Intestine and Identification of an Early T Cell Receptor β-Chain Transcript

TCR expression by human fetal intestinal intraepithelial lymphocytes (iIELs) and intestinal lamina propria lymphocytes was analyzed to address whether T cell development occurs in human fetal intestine, the diversity of human fetal iIELs, and whether human fetal iIELs may contribute to the adult iIEL repertoire. iIELs and intestinal lamina propria lymphocytes from second trimester human fetal intestine were analyzed for TCR-αβ transcripts. Rearranged TCR-α transcripts were undetectable at 14 wk in the intraepithelial lymphocytes (IELs), whereas multiple TCR-β transcripts were found at this stage. The TCR-α repertoire remained restricted relative to TCR-β at later stages, and the IEL repertoire was restricted relative to the lamina propria lymphocytes at all stages. A previously reported T early α message was the major transcript from the TCR-α locus early in gestation. A previously undescribed TCR-β transcript initiating upstream of the Dβ1 locus and spliced to Cβ1 or Cβ2 was also identified and may represent a T early β message. These results provide evidence for ongoing TCR gene rearrangement in human fetal intestine and suggest that transcription from the TCR-β locus initiates with a T early β transcript. The TCR-α repertoire (and hence the repertoire of potentially functional IELs) was limited through the second trimester.