IMPAIRED SURVIVAL OF T-CELL RECEPTOR V-GAMMA-3(-4 TRANSGENIC MICE() CELLS IN INTERLEUKIN)

The mouse epidermis contains a network of Thy-1(+) dendritic T cells. Most of these cells express a homogeneous T cell receptor (TCR) config uration (V gamma 3/ V delta 1) with only negligible junctional diversi ty. Because fetal thymocytes are precursors of these dendritic epiderm al T cells (DETC) and the addition of interleukin (IL)-4 to fetal thym ic organ cultures causes an early arrest in thymopoiesis, we examined DETC development in transgenic (tg) mice expressing IL-4 under the con trol of major histocompatibility complex class I regulatory sequences. Immunohistologic examination of epidermal sheets and polymerase chain reaction analysis of total skin RNA from IL-4 tg mice failed to revea l TCR V gamma 3(+) DETC and V gamma 3 mRNA, respectively In contrast, the sizes of TCR gamma delta subpopulations in lymphoid organs were un changed in these mice. Although the numbers and staining intensities o f TCR V gamma 3(+) thymocytes in early fetal (days 14-17) IL-4 tg mice were similar to those of littermate controls, we observed a preferent ial death of these cells in thymic organ cultures from IL-4 tg mice. W e observed further that epidermal sheets prepared from 9-day-old mice whose mothers had been treated with an IL-4-neutralizing antibody from day 12 to day 18 of pregnancy contained DETC numbers similar to those of controls. However, upon termination of the anti-IL-4 treatment, DE TC ceased to expand. We conclude that IL-4 impairs the survival of TCR V gamma 3(+) cells.