Appearance of TCR-αβ⁺CD4^-CD8^- skin intraepithelial lymphocytes in radiation bone marrow chimeras

Thymocytes expressing homogeneous TCR Vγ5/Vδ1 gene without N nucleotide addition (canonical sequence) have been reported to be positively selected in fetal thymus. Because skin intraepithelial lymphocytes (s-IEL) also express canonical sequence, it is proposed that s-IEL are generated by an epidermis- specific homing of these positive selected fetal Vγ5/Vδ1-bearing thymocytes. We have reported that positive selection of Vγ5⁺ thymocytes is not seen in AKR/J→C3H/He bone marrow chimeras. In this report, we analyzed the phenotype of donor-derived s-IEL from AKR/J→C3H/He bone marrow chimeras that appeared in the absence of positive selection of Vγ5-bearing thymocytes. We found interestingly that almost all donor-derived s-IEL in the bone marrow chimeras expressed TCR-αβ and lack expression of both CD4 and CD8. Furthermore, TCR-αβ⁺ s-IEL were detected in adult-thymectomized bone marrow chimeras, indicating that the TCR-αβ⁺ s-IEL are extrathymically derived. All these results suggest that the s-IEL expressing TCR-αβ appear extrathymically in the absence of positive selection of Vγ5/Vδ1-bearing thymocytes. Our results may also explain the contradicting result between human s-IEL, which are TCR-αβ⁺CD4^-CD8^- and murine s-IEL, and suggest the importance of extrathymic T cell differentiation pathway of the TCR-αβ lineage in immune surveillance.