Functional dichotomy between Langerhans cells that present antigen to naive and to memory/effector T lymphocytes

Abstract

The general thrust of this volume is to review the roles of accessory cells in regulating T and B lymphocytes. To that end, we have summarized the evidence that indicates the crucial role that Langerhans cells play in the induction and expression of immunity to antigens that gain access to, or arise within, skin. Langerhans cells accomplish this important goal by their abilities to (a) activate naive T cells to antigens not previously encountered by the host, and (b) activate memory/effector T cells specific for previously encountered antigens. Arguments have been advanced to support the view that the functional properties of Langerhans cells used to present antigens to naive T cells differ substantially from the properties that equip Langerhans cells to activate effector T cells. The arguments are based in part on the fact that Langerhans cells carry out these functions in two very different environments: in the epidermis, and in the draining lymph node. The arguments are also based on results of in vitro experiments that reveal distinct differences in antigen processing and presenting properties of Langerhans cells freshly obtained from mouse and human skin as compared to Langerhans cells that have been cultured in vitro for 2-3 days. We propose that freshly explanted Langerhans cells faithfully reflect the functional program of intraepidermal Langerhans cells, and are able to present antigen to memory/effector T cells that enter the epidermal compartment. To accomplish this task, epidermal LC pick up environmental antigens, process them with great efficiency, and then present them in situ, without further upregulation of "accessory" signals (cell-adhesion molecules, secretion of additional cytokines). They can carry out this function, even in the presence of TGFB--a a cytokine which is constitutively made by keratinocytes, and which we have found to profoundly inhibit antigen presentation by most other types of "professional" antigen-presenting cells. Intraepidermal Langerhans cells are also capable of carrying cutaneous antigens through the dermal epidermal junction and migrating to the draining lymph node. We further propose that cultured Langerhans cells are fated to present antigens to unprimed/naive T cells, and thereby to initiate immune responses to new cutaneous antigens. Cultured LC process antigens less efficiently than fresh cells, but their unique capacity to present antigen effectively to unprimed T cells rests chiefly on the fact that they have significantly upregulated cell surface adhesion molecules, expression of MHC molecules, and secretion of activating cytokines--the "accessory" signals that are required for arousing naive T cells.(ABSTRACT TRUNCATED AT 400 WORDS)