In vitro evidence that Langerhans cells can adopt two functionally distinct forms capable of antigen presentation to T lymphocytes

Abstract

Monodisperse suspensions of epidermal Langerhans cells (LC) have been examined for their capacity to process and present Ag immediately upon extraction from mouse epidermis (fresh LC) and after 72 h in tissue culture (cultured LC). Cultured, but not fresh, LC stimulated proliferation among autologous T cells, whereas fresh, but not cultured, LC proved to be superior at processing native OVA for presentation to an OVA peptide-specific, MHC-restricted T cell hybridoma. Cultured LC were also more effective at stimulating proliferation among allogeneic T cells. However, a significant, but difficult to quantify, component of lymphocyte activation in these assays was derived from the ability of cultured LC to stimulate autologous T cells. It has been proposed that the superior capacity of cultured LC to stimulate T cells in these assays is due to the "immaturity" of freshly prepared LC--which "mature" during the 72-h culture interval. Based on the observation that fresh LC are superior at processing native protein Ag, we would amend the currently held notion that there is a "precursor-product" relationship between fresh and cultured LC to include the fact that these populations are differentially equipped to carry out distinct physiologic functions and that fresh LC should not, therefore, be considered "immature." We propose that fresh LC (in vitro equivalents of intraepidermal LC) can process native protein Ag with great efficiency, and can present these Ag in situ to memory and effector T cells (high affinity TCR interactions). Cultured LC (in vitro equivalents of LC that have migrated from skin to draining lymph node) exchange highly efficient Ag processing for acquisition of accessory molecules (surface ligands and secreted cytokines) that promote activation of unprimed T cells (including even low affinity TCR interactions).