T cells developing in fetal thymus of T‐cell receptor α‐chain transgenic mice colonize γδ T‐cell‐specific epithelial niches but lack long‐term reconstituting potential

Summary The γδ T cells generated during mouse fetal development are absolutely dependent on their invariant T‐cell receptors (TCRs) for their function. However, there is little information on whether the epithelial homing properties of fetal T cells might also be developmentally induced by factors unrelated to TCR specificity. We have previously described TCR α‐chain transgenic (2B4 TCR‐α TG) mice, in which the transgenic TCR α‐chain is expressed early, already at embryonic day 14 (E14). These mice have a large population of ‘γδ T‐cell‐like’ CD4 –  CD8 – (double‐negative; DN) αβ T cells, some of which develop during E14–E18 contemporarily to intraepithelial lymphocytes (IELs) expressing invariant TCR‐γδ. Using the 2B4 TCR‐α TG mouse model we have been able to more precisely study the impact of a variant TCR expression on IEL development and homing. In this study we show that TCR‐α TG and TCR‐α TG crossed to TCR‐δ‐deficient mice (TCR‐α TG × TCR‐δ –/– ) carry TG TCR‐α + dendritic epidermal T cells (DETCs) and TCR‐α TG + IELs in the small intestine. The TG + DETCs develop and seed the epidermis with similar kinetics as Vγ5 + DETCs of normal mice, in contrast to the TCR‐αβ + DETCs found in TCR‐δ –/– mice. However, whereas the intestinal TCR‐α TG + IELs persist in old mice (> 20 months), the TCR‐α TG + DETCs do not. The data in this study indicate that the timing of TCR expression and thereby development during ontogeny regulates the specific homing potential for fetal T cells but not their subsequent functions and properties.