Evidence for the Extrathymic Origin of Intestinal TCRγδ+ T Cells in Normal Rats and for an Impairment of This Differentiation Pathway in BB Rats

The BB rat lyp mutation, one of its diabetes susceptibility genes, is responsible for a 5-fold decrease in the number of peripheral TCRalphabeta(+) T cells. In this study we show that TCRgammadelta(+) T cells are virtually undetectable among splenic T cells and intestinal intraepithelial T lymphocytes (IEL) of BB rats, while they account for 3 and 30% of these two T cell populations, respectively, in normal animals. It has been shown that murine IEL expressing TCRgammadelta develop extrathymically. We determined whether this is the case in rats. Athymic radiation chimeras reconstituted with normal hemopoietic precursors were devoid of donor-derived TCRalphabeta(+) T cells and TCRgammadelta(+) splenocytes but contained a normal number of TCRgammadelta(+) IEL, suggesting that in unmanipulated rats some of the TCRgammadelta(+) IEL may have an extrathymic origin. This was further supported by the observation that RAG1 transcripts are present in IEL of unmanipulated animals. No T cells developed in chimeras reconstituted with BB hemopoietic precursors, demonstrating that the BB rat lyp mutation inhibits both intrathymic and extrathymic development of TCRgammadelta(+) T cells.