Langerhans cells – dendritic cells of the epidermis

Abstract

Langerhans cells (LC) are dendritic cells of the epidermis. They are highly specialized leukocytes that serve immunogenic and tolerogenic purposes. Here, we review some aspects of LC biology, emphasizing those areas where LC are or may turn out to be special.

Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4+ T cells but are incapable of cross‐presentation

“…Capture of exogenous antigens by LCs leads to induction of CD4 1 T-cell responses [11][12][13]. However, the ability of LCs to cross-present exogenous antigens to CD8 1 T cells has been debated [14][15][16][17].…”

“…Recently, we have shown that LCs form a barrier against HIV-1; LCs capture HIV-1 through Langerin, resulting in internalization of HIV-1 into Birbeck granules and preventing subsequent HIV-1 transmission [10]. However, little is known about the role of human LCs and Langerin in antigen presentation.Capture of exogenous antigens by LCs leads to induction of CD4 1 T-cell responses [11][12][13]. However, the ability of LCs to cross-present exogenous antigens to CD8 1 T cells has been debated [14][15][16][17].…”

Insights into Langerhans cell function from Langerhans cell ablation models

“…In particular, Ralph Steinman's group [3] dissected the functional characteristics of LC starting from the seminal finding that murine epidermal LC mature into potent immunostimulatory dendritic cells (DC) in vitro. The work that followed shaped the concept of DC as professional inducers of T-cell immune responses largely by studying LC, though the term 'LC paradigm' was coined much later by Wilson and Villadangos [4].This concept assigned three key functions to LC/DC (reviewed in [5]). First, immature LC that reside in the periphery in the steady state are highly specialized in antigen uptake.…”

“…In addition, they dramatically upregulate their surface expression of co-stimulatory molecules and start to produce cytokines required for proper Th1 or Th2 instruction. Thus, by the time LC arrive in the LN, they have acquired the surface phenotype of a 'functionally' mature DC capable of activating naive T cells and thereby initiating an adaptive immune response specifically tailored to fight off the invading cutaneous pathogen [5].The LC paradigm has been expanded to include LC that migrate to skin-draining LN in the steady state in the absence of activating stimuli where they present self-peptides to T cells [10][11][12][13][14]. This steady-state presentation of self-antigens has been proposed to eliminate self-reactive T cells and provide a mechanism of peripheral tolerance [15,16].…”

CCL19 as an adjuvant for intradermal gene gun immunization in a Her2/neu mouse tumor model: improved vaccine efficacy and a role for B cells as APC

“…8,31 It is generally believed that DNA-coated gold particles target APC in the upper layer of the skin where they exist at a very high density. 4,5,[32][33][34][35] Furthermore, local injury by gene gun particle bombardment may induce a local inflammatory environment supporting DC maturation and subsequent T-cell activation. 4,5,[36][37][38] Unexpectedly, after gene gun application, Her2/ neu peptide-specific CD8 þ g-IFN T-cell responses were lower after coadministration of CCL19, despite better tumor protection compared with Her2/neu alone.…”