0000000000067793
AUTHOR
Talkea Schmidt
T cell killing by tolerogenic dendritic cells protects mice from allergy.
It is well established that allergy development can be prevented by repeated low-dose exposure to contact allergens. Exactly which immune mechanisms are responsible for this so-called low zone tolerance (LZT) is not clear, although CD8⁺ suppressor T cells are known to have a role. Here, we show that TNF released by tolerogenic CD11⁺CD8⁺ DCs located in skin-draining lymph nodes is required and sufficient for development of tolerance to contact allergens in mice. DC-derived TNF protected mice from contact allergy by inducing apoptosis in allergen-specific effector CD8⁺ T cells via TNF receptor 2 but did not contribute to the generation and function of the regulatory T cells associated with LZ…
Myeloid cell populations and fibrogenic parameters in bleomycin- and HOCl-induced fibrosis
Mouse models resembling systemic sclerosis can be chemically induced by application of bleomycin or hypochloric acid (HOCl). To date, little is known about inflammatory cells and their potential role in scleroderma (Scl)-related fibrosis. Therefore, we compared both Scl models to define the early immune cell subsets in relation to fibrosis-related parameters. Both agents induced a significant increase in dermal thickness and collagen deposition after 4 weeks, as hallmarks of Scl. However, clinical skin thickness, densely packed, sirius red-stained collagen bundles and collagen cross-links were more pronounced in HOCl-induced Scl. In parallel, there was a significant upregulation of procolla…
Investigation of Sudan IV staining areas in aortas of infants and children: Possible prelesional stages of atherogenesis
Although atherosclerosis in infants and children is generally acknowledged, the temporal and spatial sequence of LDL insudation, modification and intimal monocyte accumulation has not been systematically studied. We have investigated herein very early stages of lesion formation in human aortas of individuals up to the age of 15 years. Aortic specimens from 61 cases (37 male, 24 female) were examined. 34 cases were1 year old, 16 cases were between 1 and 5 years old, and 11 cases were between 6 and 15 years old. Areas preselected under a dissection microscope after Sudan IV staining were investigated in depth by immunohistochemical staining for apolipoprotein B, monocytes/macrophages, smooth …
Epicutaneous and Oral Low-Zone Tolerance Protects from Colitis in Mice
Tolerance to environmental antigens that encounter the organism at interfaces like skin or gut prevents deleterious systemic immune responses. The aim of this study was to analyze whether and how low doses of haptens, by entry through the skin or gastrointestinal tract, affect the outcome of the predominantly Th1/Th17-mediated 2,4,6-trinitro-benzenesulfonic acid-induced colitis, which mimics an autoimmune bowl disease in man. Epicutaneous and oral applications of low doses of the allergen resulted in the induction of low-zone tolerance (LZT) and protected from colitis development, demonstrated by a significantly reduced inflammatory response of the gut in vivo. In line with this observation…
Crosstalk of regulatory T cells and tolerogenic dendritic cells prevents contact allergy in subjects with low zone tolerance
Background Allergic contact dermatitis is one of the most common occupational diseases. A main protective mechanism in those who do not develop allergic contact dermatitis is tolerance induction by repeated exposure to low doses of contact allergen, which is termed low zone tolerance (LZT). The mechanisms that determine the tolerance induction in subjects with LZT are still elusive. Objective We performed analysis of the role of CD4 + CD25 + forkhead box protein 3 (FOXP3)–positive regulatory T (Treg) cells and dendritic cells (DCs) in mice with LZT. Methods Mechanisms of tolerance induction were analyzed in a murine model of LZT by using FOXP3 and IL-10 reporter mice, as well as mice that a…