CHARACTERISTICS OF FETAL THYMUS-DERIVED T-CELL RECEPTOR-GAMMA-DELTA INTESTINAL INTRAEPITHELIAL LYMPHOCYTES

We have previously demonstrated that grafting of CBF1(H-2(b/d)) fetal. thymus (FTG) under the kidney capsule of congenitally athymic nude mi ce of BALB/c background (H-2(d)) generates a substantial number of T c ell receptor (TCR) gamma delta intestinal intraepithelial lymphocytes (IEL) that were of FTG origin (H-2(b+)) (see accompanying report). Her e we investigated the characteristics of these FTG-derived TCR gamma d elta IEL and compared them to the extrathymically derived TCR gamma de lta IEL found in nude mice. Phenotypically, FTG-derived TCR gamma delt a IEL were similar to their extrathymically derived counterparts in th at most were Thy-1(-), CD5(-) and CD8 alpha alpha (homodimer). V gamma and V delta gene usage in thymus-derived and extrathymically derived TCR gamma delta IEL were found to be virtually the same. Functionally, FTG-derived TCR gamma delta IEL were similar to the TCR gamma delta I EL found in euthymic mice as both were relatively anergic to TCR cross -linking in vitro. However, FTG-derived TCR gamma delta IEL differed s lightly from extrathymically derived TCR gamma delta IEL, which were c ompletely nonresponsive to the same in vitro stimulation. Overall, the se findings support the view that FTG-derived and extrathymically deri ved TCR gamma delta IEL are almost indistinguishable. Lastly, we demon strate that despite their thymic origin, development of FTG-derived TC R gamma delta IEL partially takes place extrathymically; that is posit ive selection of FTG-derived V delta 4 IEL occurs extrathymically. In addition, we demonstrate that the CD8 molecule is not necessary for de velopment and homing of FTG-derived TCR gamma delta IEL. This later fi nding suggests that the CD8 alpha alpha molecule develops extrathymica lly for FTG-derived CD8 alpha alpha TCR gamma delta IEL.