Langerhans Cells Are Required for Efficient Presentation of Topically Applied Hapten to T Cells

Abstract

Dendritic cells (DC) play a pivotal role in the control of T cell immunity due to their ability to stimulate naive T cells and direct effector function. Murine and human DC are composed of a number of phenotypically, and probably developmentally, distinct subsets, which may play unique roles in the initiation and regulation of T cell responses. The skin is populated by at least two subsets of DC: Langerhans cells (LC), which form a contiguous network throughout the epidermis, and dermal DC. LC have classically been thought vital to initiate T cell responses to cutaneous Ags. However, recent data have highlighted the importance of dermal DC in cutaneous immunity, and the requirement for LC has become unclear. To define the relative roles of LC and dermal DC, we and others generated mouse models in which LC were specifically depleted in vivo. Unexpectedly, these studies yielded conflicting data as to the role of LC in cutaneous contact hypersensitivity (CHS). Extending our initial finding, we demonstrate that topical Ag is inefficiently transported to draining lymph nodes in the absence of LC, resulting in suboptimal priming of T cells and reduced CHS. However, dermal DC may also prime cutaneous T cell responses, suggesting redundancy between the two different skin DC subsets in this model.

Insights into Langerhans cell function from Langerhans cell ablation models

“…The choice of hapten does not seem to be critical since the Dutch mice also have reduced CHS to oxazalone [35]. Rather, it appears that the timing of DT administration can affect the outcome since French mice treated with DT only on day À1 develop diminished CHS responses similar to the Dutch mice [36,37]. Thus, even though the mice have not been compared side-by-side in the same experiment and minor differences may still exist, it appears that the two Langerin-DTR lines behave similarly when examined using a comparable protocol.…”

Imunopatologia da dermatite de contato alérgica

“…Until then the role of LC in sensitization had been defined as inducer, indifferent or suppressor. In 2007, Bennett et al 76 returned to their model and demonstrated that antigens are not properly transported to lymph nodes in the absence of LC and concluded that it decreases sensitization to antigens, confirming their findings in the first trial. They attributed the following to the differences found in the other studies: 1) perennial absence of LC in the model of Kaplan et al and 2) the use of high concentrations of allergens in the other studies.…”

“…That trial indicates that langerin dermal DC and not LC and langerin dermal DC are the main responsible for the development of ACD. However, Bursch et al 80 and Bennett et al 76 used a similar system and failed to induce ACD with low concentrations of oxazolone in the fourth week after ablation, time period during which only langerin dermal DC have returned to normal, indicating that LC are necessary for sensitization. A possible conciliatory explanation lies in the concentration of haptens applied to sensitization.…”

“…A possible conciliatory explanation lies in the concentration of haptens applied to sensitization. Bacci et al 84 and Bennett et al 76 suggest that at higher concentrations the antigen is captured by both LC and dermal DC, which induce the generation of an effector response in regional lymph nodes, and that at lower concentrations the antigen is especially captured by LC, which induce the process by themselves.…”

“…Induced depletion of these cells by topical corticosteroids, UVB radiation or their selective ablation in experimental models with previously sensitized mice did not result in reducing the allergic response. 73,74,76,85 It is believed that macrophages, keratinocytes and mast cells also act as antigen-presenting cells. 86.87 The role of these presenting cells, including LC, in the effector phase of ACD is still under study.…”