THYMUS INFLUENCES THE DEVELOPMENT OF EXTRATHYMICALLY DERIVED INTESTINAL INTRAEPITHELIAL LYMPHOCYTES

Overwhelming evidence suggests that the majority of murine small intes tinal intraepithelial lymphocytes (IEL) are extrathymically derived.Th ese IEL include those with T cell receptor (TCR) gammadelta and some T CR alphabeta (CD8alphaalpha and Thy-1-). In contrast, congenitally ath ymic nude mice have low numbers of gammadelta TCR IEL as well as very few alphabeta TCR IEL, far less than that would be expected if one ass umes that gammadelta TCR IEL and alphabeta TCR (CD8alphaalpha and Thy- l-) IEL in euthymic mice are extrathymically derived. To examine this discrepancy, we followed extrathymic IEL differentiation in IEL of day 3-thymectomized (NTX) mice as another athymic mouse model and found t hat gammadelta TCR IEL and extrathymically derived alphabeta TCR IEL i n NTX mice are markedly reduced, almost to the level of nude mice. We further show that it is probably the absence of a thymic stroma that i s responsible for the lower amounts of extrathymically derived IEL in nude mice, as the low amounts can be corrected to euthymic levels by s yngeneic fetal thymus grafting but not by direct injection of F1 thymo cytes. Lastly, unlike TCR/CD3+ extrathymically derived IEL, we noted a large proportion of extrathymic CD3-CD8- and CD3-CD8+IEL; they were t hreefold more frequent in nude and NTX than in euthymic mice. This sug gests that the thymus influences extrathymically derived IEL in its de velopment from CD3- to CD3+ at the small intestinal epithelium.