Specific stabilization of the 4F7 molecule on dendritic cells by contact allergens

Abstract

Our laboratory has recently developed the monoclonal antibody 4F7 which recognizes a molecule on dendritic cells in the dermis of mice that is upregulated after application of contact allergens in vivo. Furthermore, this antibody detects an antigen on dendritic cells in spleen, lymph nodes and colon. In order to study the influence of contact allergens on the surface expression of the 4F7 molecules on dendritic cells, FACScan analysis of splenic dendritic cells was carried out after in vitro application of contact allergens. Freshly isolated splenic dendritic cells were found to be positive for 4F7, 33D1, N418 (CD11c) and MHC class II. After overnight culture the expression of the dendritic cell-specific molecules 4F7 and 33D1 was decreased. This downregulation was not inhibited by the addition of the cytokines TNF-alpha or GM-CSF during in vitro culture. However, in vitro treatment of freshly isolated dendritic cells with the contact allergen 2,4-dinitrofluorobenzene prevented this downregulation of the 4F7 surface molecules. The same effect was observed after treatment with other contact allergens (1-chloro-2,4-dinitrobenzene or potassium dichromate). Treatment with the irritant substance sodium dodecyl sulphate, the lectins concanavalin and lipopolysaccharide or the phorbol ester PMA did not prevent the downregulation of 4F7 and 33D1. Moreover, the influence of contact allergens on the expression of the molecules 4F7 and 33D1 was not inhibited by the protein synthesis inhibitor cycloheximide. No effects of contact sensitizers were detectable on the expression of MHC class II molecules or the costimulatory molecules B7 and heat-stable antigen. Our results show a specific stabilizing effect of contact allergens on the dendritic cell-specific molecules 4F7 and 33D1 independent of de novo protein synthesis.

TNF-α-dependent maturation of local dendritic cells is critical for activating the adaptive immune response to virus infection

“…Maturation and proper education of DC depends on microbial stimulation, which occurs during virus uptake and in many cases depends on recognition of patterns inherent to the pathogen (25)(26)(27). Furthermore, other signals such as cytokines synergize with microbial stimulation to facilitate DC maturation (28,29).…”

“…This model does not exclude the role of other cytokines and molecules in the maturation of DC. In fact, IL-1 and CD40 have both been shown to stimulate DC maturation and may work together with TNF for efficient immune activation (28,39). Furthermore, in this model, the CD11c ϩ DC or myeloid lineage DC may also elaborate TNF after virus uptake (22), thus amplifying TNF-mediated maturation locally and in the draining lymph node.…”

Keratinocytes in Inflammatory Skin Diseases

“…These molecules induce a direct inflammatory activation of keratinocytes, resulting in the expression of cytokines, chemokines and adhesion molecules [8,9,10]. During cutaneous allergic responses to haptens, keratinocytes produce TNF-α, IL-1 and GM-CSF, which have pleiotropic effects and can activate various cell populations of the skin, including Langerhans cells and dermal endothelial cells [11,12]. TNF-α released by hapten-activated keratinocytes can act in an autocrine manner on keratinocytes themselves, and induce intercellular adhesion molecule (ICAM)-1 and CXCL8/IL-8 expression observed in vivo in these cells during ACD reactions [13].…”

Molecular Cloning of a Dendritic Cell-associated Transmembrane Protein, DC-HIL, That Promotes RGD-dependent Adhesion of Endothelial Cells through Recognition of Heparan Sulfate Proteoglycans

“…DC are widely distributed but comprise only a minuscule fraction (typically Ͻ5%) of the total cell population of a given peripheral tissue. After capturing antigens, tissue DC undergo maturation, losing endocytic capacity but acquiring increased immunostimulatory capacity (2). During maturation, DC migrate from peripheral tissues to T cell areas of secondary lymphoid organs where they activate T cells (2)(3)(4).…”

“…After capturing antigens, tissue DC undergo maturation, losing endocytic capacity but acquiring increased immunostimulatory capacity (2). During maturation, DC migrate from peripheral tissues to T cell areas of secondary lymphoid organs where they activate T cells (2)(3)(4). Thus, DC migration is a critical step in initiating antigenspecific immune responses.…”