TCR EXPRESSION IN HUMAN FETAL INTESTINE AND IDENTIFICATION OF AN EARLY T-CELL RECEPTOR BETA-CHAIN TRANSCRIPT

TCR expression by human fetal intestinal intraepithelial lymphocytes ( iIELs) and intestinal lamina propria lymphocytes was analyzed to addre ss whether T cell development occurs in human fetal intestine, the div ersity of human fetal iIELs, and whether human fetal iIELs may contrib ute Ito the adult iIEL repertoire. iIELs and intestinal lamina propria lymphocytes from second trimester human fetal intestine were analyzed for TCR-alpha beta transcripts. Rearranged TCR-alpha transcripts were undetectable at 14 wk in the intraepithelial lymphocytes (IELs), wher eas multiple TCR-beta transcripts were found at this stage. The TCR-al pha repertoire remained restricted relative to TCR-beta at later stage s, and the IEL repertoire was restricted relative to the lamina propri a lymphocytes at all stages. A previously reported T early alpha messa ge was the major transcript from the TCR-alpha locus early in gestatio n. A previously undescribed TCR-beta transcript initiating upstream df the D beta 1 locus and spliced to C beta 1 or C beta 2 was also ident ified and may represent a T early beta message. These results provide evidence for ongoing TCR gene rearrangement in human fetal intestine a nd suggest that transcription from the TCR-beta locus initiates with a T early beta transcript. The TCR-alpha repertoire (and hence the repe rtoire of potentially functional IELs) was limited through the second trimester.