Characteristics of fetal thymus‐derived T cell receptor γδ intestinal intraepithelial lymphocytes

Abstract

We have previously demonstrated that grafting of CBF1 (H-2b/d) fetal thymus (FTG) under the kidney capsule of congenitally athymic nude mice of BALB/c background (H-2d) generates a substantial number of T cell receptor (TCR) gamma delta intestinal intraepithelial lymphocytes (IEL) that were of FTG origin (H-2b+) (see accompanying report). Here we investigated the characteristics of these FTG-derived TCR gamma delta IEL and compared them to the extrathymically derived TCR gamma delta IEL found in nude mice. Phenotypically, FTG-derived TCR gamma delta IEL were similar to their extrathymically derived counterparts in that 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 IEL found in euthymic mice as both were relatively anergic to TCR cross-linking in vitro. However, FTG-derived TCR gamma delta IEL differed slightly from extrathymically derived TCR gamma delta IEL, which were completely nonresponsive to the same in vitro stimulation. Overall, these findings support the view that FTG-derived and extrathymically derived TCR gamma delta IEL are almost indistinguishable. Lastly, we demonstrate that despite their thymic origin, development of FTG-derived TCR gamma delta IEL partially takes place extrathymically; that is positive selection of FTG-derived V delta 4 IEL occurs extrathymically. In addition, we demonstrate that the CD8 molecule is not necessary for development and homing of FTG-derived TCR gamma delta IEL. This later finding suggests that the CD8 alpha alpha molecule develops extrathymically for FTG-derived CD8 alpha alpha TCR gamma delta IEL.