CD5- dendritic epidermal T cells are derived from CD5+ precursor cells

Murine Thy-1+, TcR V gamma 3/V delta 1+ dendritic epidermal T cells (DETC) differ from most other T cell subsets by the absence of CD4 and CD8 antigens as well as the lack of CD5 expression. To see whether negativity for those antigens is an intrinsic feature of a given T cell population or if such triple-negative T cells go through a maturational stage where they express these antigens, we determined the phenotype of TcR V gamma 3+ fetal thymocytes which are the precursor cells of DETC. We found that TcR V gamma 3+ fetal thymocytes phenotypically differ from mature DETC in that they are CD5+, mostly CD8+ and partly CD4+. The injection of fetal thymic suspensions containing TcR V gamma 3+/CD5+ (but not TCR V gamma 3+/CD5-) thymocytes into Thy-1-disparate athymic nude mice resulted in the appearance of donor-type TcR V gamma 3+/CD5- dendritic cells in the recipients' epidermis, indicating that TcR V gamma 3+ thymocytes are indeed the precursors of CD5- DETC. Tracing CD5 expression on DETC precursors during their intrathymic maturation and their migration to the fetal skin, we found that (i) the earliest DETC precursor cells as defined by TcR V gamma 3 expression express high levels of CD5 antigen (day 15 of gestation), (ii) after day 16 of gestation 70% of TcR V gamma 3+ thymocytes express high and 30% express intermediate levels of CD5, (iii) TcR V gamma 3+ cells in the fetal blood express low levels of CD5, (iv) the first TcR V gamma 3+ cells entering the epidermis express very low levels of this antigen and (v) TcR V gamma 3+ epidermal cells later than day 19 of gestation are CD5-. A similar down-regulation of CD5 expression on DETC precursors was also noted when TcR V gamma 3+ cells were cultured in vitro. Even the addition of PMA and ionomycin, which up-regulates CD5 expression on TcR alpha/beta-bearing thymocytes and lymph node T cells, could not prevent CD5 down-regulation on DETC precursors. The described cell system may serve as a useful tool in further experiments aimed to clarify the function of the CD5 glycoprotein as well as the mechanism(s) regulating its expression.