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

Abstract

We have previously demonstrated that grafting of CBF1(H‐2^b/d) fetal thymus (FTG) under the kidney capsule of congenitally athymic nude mice of BALB/c background (H‐2^d) generates a substantial number of T cell receptor (TCR) γδ intestinal intraepithelial lymphocytes (IEL) that were of FTG origin (H‐2^b+) (see accompanying report). Here we investigated the characteristics of these FTG‐derived TCR γδ IEL and compared them to the extrathymically derived TCR γδ IEL found in nude mice. Phenotypically, FTG‐derived TCR γδ IEL were similar to their extrathymically derived counterparts in that most were Thy‐1 ⁻, CD5⁻ and CD8αα (homodimer). Vγ and Vδ gene usage in thymus‐derived and extrathymically derived TCR γδ IEL were found to be virtually the same. Functionally, FTG‐derived TCR γδ IEL were similar to the TCR γδ IEL found in euthymic mice as both were relatively anergic to TCR cross‐linking in vitro. However, FTG‐derived TCR γδ IEL differed slightly from extrathymically derived TCR γδ IEL, which were completely nonresponsive to the same in vitro stimulation. Overall, these findings support the view that FTG‐derived and extrathymically derived TCR γδ IEL are almost indistinguishable. Lastly, we demonstrate that despite their thymic origin, development of FTG‐derived TCR γδ IEL partially takes place extrathymically; that is positive selection of FTG‐derived Vδ4 IEL occurs extrathymically. In addition, we demonstrate that the CD8 molecule is not necessary for development and homing of FTG‐derived TCR γδ IEL. This later finding suggests that the CD8αα molecule develops extrathymically for FTG‐derived CD8αα TCR γδ IEL.