T Cell-Mediated Terminal Maturation of Dendritic cells

Abstract

Numerous investigators have supported, with compelling evidence, the concept that the activation of naive T cells occurs primarily through antigens (Ag) presented by a distinct class of leukocytes known as dendritic cells (DC). As skin biologists, our own efforts have focused on Langerhans cells (LC), a unique population of DC that resides normally within the epidermis of skin and whose identification even predates knowledge about DC by more than one century. Three years ago, we initiated a program to develop long-term DC lines from the epidermis of mice, largely to accommodate the cellular homogeneity that is required for molecular biologic techniques, but also to facilitate the economic use of laboratory animals. Two concepts guided these efforts: 1) cells derived during the perinatal period would possess a highest proliferative potential, and 2) GM-CSF, which had promoted the survival and maturation of LC cultured by other investigators, would be essential. Our efforts were ultimately rewarded by the development of stable DC lines, termed the “XS series”, from specimens of epidermis in newborn BALB/c mice (1). These XS DC lines resemble resident LC in many respects, including: a) their dendritic morphology (1), b) Ag presenting capacity (1,2), and c) cytokine and cytokine receptor mRNA profiles (3–6). Importantly, our original XS cell cultures were “contaminated” by fibroblastoid cells, the “NS series,” which could be removed through their selective sensitivity to treatment with trypsin. Once this was accomplished, however, proliferation by the XS cells diminished substantially. We have determined subsequently that XS52 cells require for their optimal growth not only GM-CSF, which was added continuously to XS cell cultures, but also CSF-1, which was secreted in relatively large amounts by the NS cells (4). These XS lines and similar DC lines developed since that time have proven to be useful tools in our efforts to characterize the function of DC.