Induction of Fc epsilon R2/CD23 on human epidermal Langerhans cells by human recombinant interleukin 4 and gamma interferon.

Abstract

Recently, IgE molecules have been demonstrated on Langerhans cells (LC) frominvolved and, to a much lesser extent, in uninvolved skin of patients with atopic dermatitis, but not on LC from nonatopic individuals (1, 2). This finding indicated that, in atopic dermatitis, LC are induced to either synthesize receptors for IgE and/or to acquire IgE-binding FceR2 split products. As opposed to the selective expression of FcER1 by basophils and mast cells, low affinity Fc-IgE receptors (FceR2/CD23) have been described on numerous cell types including B and T cells, eosinophils, platelets, and monocytes (3, 4). The most recent finding that an anti-FceR2 mAb can inhibit the binding of IgE-coated ox erythrocytes to LC from atopic dermatitis patients (5) supports the contention that the presence of IgE on LC surfaces in this disease results from the binding of IgE to FceR2 . For many of the above cells, FceR2/CD23 expression is not a constitutive event but rather regulated by soluble mediators including human rIL-4 (hrIL-4 ; 6, 7), human rIFN-y (hrIFN -y; 6, 8), and PMA (8).To establish an in vitro model for studying putative T lymphocyte-LC interactions in atopic dermatitis, we asked in this study whether these substances can induce FceR2/CD23 expression on LC isolated from the epidermis of nonatopic individuals and, if so, whether such LC are capable of IgE binding . mAbs against CDla antigen (phycoerythrin [PE]-labeled T6/RDI, IgGI, Coultertronics, Krefeld, FRG; FITC-labeled OKT6, IgGI, Orthopharmaceuticals, Raritan, NJ) were used for LC labeling (9). M-L25 (IgGI ; Institute for Immunology, Munich, FRG) (10) and 3-5 (IgGl ; kindly provided by T. Kishimoto, Institute of Molecular and Cellular Biology, University of Osaka, Japan) (11) are both anti-CD23 mAbs. BIP-1 (IgGI ; Institute of General and Experimental Pathology, University of Vienna, Austria) (12), anti-IgM mAb AF-6 (IgGI ; Immunotech, Marseille, France), and anti-IgG mAb 8a4 (10 hg/ml) (IgGI, Immunotech,

Peptide blocking of IgE/receptor interaction: possibilities and pitfalls

“…The binding of multivalent antigen to the V-region of receptoroccupied IgE causes the aggregation of adjacent receptors. Mast cells and basophils respond by secretion of a wide spectrum of diverse proinflammatory mediators, including histamine, prostaglandins, leukotrienes, cytokines (including interleukins [IL]-3, -4, -5, -6, -10, -13, tumor necrosis factoralpha (TNF-a), granulocyte/macrophage colonystimulating factor (GM-CSF), and several serine proteases, the function of which is uncertain (16)(17)(18). These mediators not only cause the acute phase of the allergic response but also play an important role in the selective activation of inflammatory cell subpopulations.…”

“…These mediators not only cause the acute phase of the allergic response but also play an important role in the selective activation of inflammatory cell subpopulations. Via the secretion of IL-4, IgE-activated mast cells/basophils induce upregulation of MHC class II and FCj^RII molecules and stimulate antibody class-switching in B cells to the IgE isotype (18)(19)(20)(21). Tlierefore, an upregulatory feedback occurs which amplifies the response to allergen.…”

Pathophysiology of itching in urticaria and atopic dermatitis

“…The IgE bound to mast cells and basophilic granulocytes is involved in the pathogenesis of the immediate hypersensitivity reaction, including the late-phase reaction, but it is not proved that these reactions are involved in the pathogenesis of AD, although it has been suggested (62). Another possible role for IgE in AD is suggested by the finding of IgE bound via low-affinity Fc-IgE receptors (Fc,R2/CD23) on Langerhans' cells in involved skin, and to a lesser extent in uninvolved skin, of AD patients with elevated serum IgE levels (63)(64)(65)(66). Epidermal Langerhans' cells may bind and present allergens to T lymphocytes, inducing an allergenspecific inflammatory response (63,67).…”

The role of alveolar macrophages and dendritic cells in allergic airway sensitization

“…In atopic patients, they may have the ability to induce type 2 cytokine secretion profiles in Th cells. On the other hand, supernatants of activated Th2 cells strongly enhance expression of the low-affinity IgE-receptor (Fc,RII/CD23) on the cell surface of APC in vitro (12); this is explained predominantly as another effect of the Th2-derived cytokine IL-4 (13, 14). However, the Th2-like production profile does not appear to be an intrinsic property of the peptide-specific T-cell populations.…”