T cell control in autoimmune bullous skin disorders
Michael Hertl, … , Rüdiger Eming, Christian Veldman
Michael Hertl, … , Rüdiger Eming, Christian Veldman
Published May 1, 2006
Citation Information: J Clin Invest. 2006;116(5):1159-1166. https://doi.org/10.1172/JCI28547.
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Review Series

T cell control in autoimmune bullous skin disorders

Abstract

Autoimmune bullous disorders are a group of severe skin diseases characterized clinically by blisters and erosions of skin and/or mucous membranes. A hallmark of these disorders is the presence of IgG and occasionally IgA autoantibodies that target distinct adhesion structures of the epidermis, dermoepidermal basement membrane, and anchoring fibrils of the dermis. This Review focuses on the potential role of autoreactive T cells in the pathogenesis of these disorders. Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are the best-characterized bullous disorders with regard to pathogenesis and T cell involvement. Activation of autoreactive T cells in PV and BP is restricted by distinct HLA class II alleles that are prevalent in individuals with these disorders. Autoreactive T cells are not only present in patients but can also be detected in healthy individuals. Recently, a subset of autoreactive T cells with remarkable regulatory function was identified in healthy individuals and to a much lesser extent in patients with PV, suggesting that the occurrence of autoimmune bullous disorders may be linked to a dysfunction of Tregs.

Authors

Michael Hertl, Rüdiger Eming, Christian Veldman

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Figure 3

T cell involvement in the immune pathogenesis of PV.

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T cell involvement in the immune pathogenesis of PV. PV is the prototype...
PV is the prototype of an autoantibody-mediated immunobullous skin disorder and is characterized by a loss of intraepidermal adhesion primarily caused by autoantibodies belonging to the IgG4 and, to a lesser extent, IgG1 subclasses specific for Dsg3 and Dsg1, components of the desmosomal adhesion complex of epidermal keratinocytes that are connected to the keratin cytoskeleton through interaction with the intracellular plaque proteins plakoglobin (PKG) and desmoplakin (DP; inset). IgG production by autoreactive B cells is presumably regulated by Dsg3- and Dsg1-reactive Th1 and Th2 cells. The Dsg3-reactive Th cells recognize epitopes of the Dsg3 ectodomain in association with the HLA class II alleles HLA-DRβ1*0402 and HLA-DQβ1*0503 presented by APCs including dendritic cells and B cells. Dsg3-reactive Th cells that recognize identical epitopes are also found in healthy carriers of the aforementioned PV-associated HLA class II alleles. Thus Tregs may be critical in maintaining peripheral B cell tolerance to Dsg3. This contention is supported by the finding that Dsg3-reactive Tr1s are more frequently detected in healthy individuals than in patients with PV.