Browsing by Author "Fuchs, Tina"

Recent evidence indicates the presence of macrophage subpopulations that express the TCR alpha beta in two major inflammatory diseases, tuberculosis and atherosclerosis. Inflammation is also a well-established attribute of cancer progression and macrophages are one of the major immune cells that infiltrate tumors. Here, we demonstrate that the macrophage-TCR alpha beta is expressed in the tumor microenvironment of human and murine malignancies. We identify TCR alpha beta(+) macrophages in each case of four randomly selected distinct human tumor entities. In human tumor tissues, the TCR alpha beta expressed by macrophages in the tumor microenvironment is a combinatorial and individual-specific immune receptor. Furthermore, we routinely find TCR alpha beta(+) macrophage subpopulations in experimental tumors (TS/A, mammary adenocarcinoma) which we induced both in normal mice and mice deficient in the macrophage receptor stabilin-1. Expression of the combinatorial murine tumor macrophage TCRotS is individual-specific and independent of stabilin-1. These results demonstrate that TCR alpha beta expression is a characteristic feature of macrophages in the tumor microenvironment and identify an as yet unrecognized flexible element in the macrophage-based host response to tumors. (C) 2015 Elsevier GmbH. All rights reserved.

Recent evidence indicates that monocytes and macrophages express T cell receptor (TCR)alpha beta-like combinatorial immune receptors. Here, we demonstrate the presence of a second recombinatorial immunoreceptor, which is structurally based on the TCR gamma- and delta-chains, in human and murine monocytes and differentially activated macrophages (referred to here as TCRLm gamma delta). In vitro, infection of macrophages with mycobacteria and gram positive or gram negative bacteria induced expression of donor-specific and differential TCRLm V delta repertoires indicating that the novel immunoreceptor represents a dynamic flexible host defense system that responds to bacterial challenge. In vivo, we find that TCRLm gamma delta bearing macrophages, which express highly restricted repertoires of the antigen-binding V delta chain, accumulate in the cerebrospinal fluid in acute bacterial meningitis and in advanced lesions of atherosclerosis. These results identify an as yet unrecognized monocyte/macrophage subpopulation that bears combinatorial TCRLm gamma delta immune receptors, and is associated with both acute and chronic inflammatory diseases. Moreover, they indicate that the monocytic lineage uses the same bipartite system of TCR alpha beta/TCR gamma delta-based combinatorial immune receptors that is present in T cells. Our findings suggest specific roles of monocytes/macrophages in various inflammatory conditions and lend further evidence that flexible immune recognition in higher vertebrates operates on a broader cellular basis than previously thought. (c) 2013 Published by Elsevier GmbH.

Macrophages play a central role in host defense against mycobacterial infection and anti-TNF therapy is associated with granuloma disorganization and reactivation of tuberculosis in humans. Here, we provide evidence for the presence of a T cell receptor (TCR) alpha beta based recombinatorial immune receptor in subpopulations of human and mouse monocytes and macrophages. In vitro, we find that the macrophage-TCR alpha beta induces the release of CCL2 and modulates phagocytosis. TNF blockade suppresses macrophage-TCR alpha beta expression. Infection of macrophages from healthy individuals with mycobacteria triggers formation of clusters that express restricted TCR V beta repertoires. In vivo, TCR alpha beta bearing macrophages abundantly accumulate at the inner host-pathogen contact zone of caseous granulomas from patients with lung tuberculosis. In chimeric mouse models, deletion of the variable macrophage-TCR alpha beta or TNF is associated with structurally compromised granulomas of pulmonary tuberculosis even in the presence of intact T cells. These results uncover a TNF-regulated recombinatorial immune receptor in monocytes/macrophages and demonstrate its implication in granuloma formation in tuberculosis.

A 65 year old man suffered from edema of his penis and scrotum 30 min after investigation of the bladder using a Tiemann catheter, natural latex gloves, and Instillagel as lubricant. The skin lesions lasted for 2 days. This reaction occurred a second time after catheterization of the bladder. At first the diagnosis of a latex allergy was assumed. To confirm this diagnosis, skin prick tests and intracutaneous tests using natural latex milk extracts were performed. The intracutaneous tests turned out to be positive. The specific IgE for latex was analyzed using the CAP method and showed a positive result (1.42 KU/l,CAP class 2). To prove the clinical relevance of these findings, a provocation test was performed by wearing natural latex gloves for 30 min. Surprisingly, the provocation test caused no symptoms, indicating that, at present, the patient suffers from latex sensitization rather than a clinically relevant natural latex allergy. Further investigation of other suspected agents, such as the catheter and the lubricant, revealed that lidocaine, a component of Instillagel, was the substance most presumably responsible for causing the skin reactions. Additional patch tests with different local anesthetics confirmed these findings. We were also able to demonstrate a skin reaction to cinchocaine. Despite the similarity in the side chains the observed patch test reactions are not to be interpreted as immunological cross-reactions. Hypersensitivity to local anesthetics is a rare phenomenon, whereas natural latex allergy is frequent. Therefore, when the apparent symptoms are more plausibly explained by a more common disease (e.g., latex allergy),the likeliest diagnosis of a bona fide allergy to local anesthetics could easily be missed. However, the correct diagnosis is of particular importance to patients,as contact dermatitis to local anesthetics could sometimes also induce immediate type reactions when applied parenterally. This case demonstrates unequivocally that all suspected substances should be investigated by different diagnostic methods, including provocation tests, in order to make the right diagnosis.

A 23-year-old woman presented with plant-like skin lesions on her neck after a black henna tattoo which was applied one week ago. She showed a lichenoid reaction which followed the pattern of the initial tattoo. The patient has no evidence for an allergic contact dermatitis in her history. Patch testing was performed with the DKG standard series, hydroquinone and a light red henna paste bought in Germany. Positive reactions to p-phenylenediamine (PPD), N-Isopropyl-N ' -phenyl-p-phenylenediamine (IPPD) and to hydroquinone, but not to henna paste were found. However the exact composition of the black henna paste used at the beach of Ibiza could not be determined. Thus we can only speculate that the paste was mixed with PPD. PPD is often mixed with henna to produce a more intense colouration and to reduce the time of fixation. Allergic contact dermatitis to pure henna is very rare. In contrast to PPD which is a strong sensitizer Lawson which is the main coloring constitute of henna has a weak sensitization potency. Therefore is it justified to suppose that our patient has been sensitized to PPD and hydroquinone by applying henna paste possible mixed with PPD and hydroquinone to her skin.

Between 1985 and 2001 a panel of 30 experts (dermatologists and chemical scientist from university, industry and federal offices) evaluated the allergenic potential of 244 chemical substances or chemicals identified as ingredients of natural products. The evaluation process was based on published evidence regarding effects on man, experimental studies, and structure-activity considerations. Category "A" comprised significant contact allergens. Chemicals for which reliable reports regarding sensitizing properties or cross-reactivity were available were ranked in group "B", whereas chemicals with doubtful sensitizing properties and insignificant allergens were classified as "C". The tabulated review comprises 98 substances of category "A", 77 of "B" and 69 of grade "C".

Chronic urticaria, recurrent angioedema and non-allergic asthma may be due to pseudoallergic reactions to food ingredients. For atopic dermatitis and gastrointestinal symptoms the role of these non-allergic reactions is discussed controversially. Pseudoallergic reactions can be elicited by food additives as well as naturally occurring food components. An altered histamine metabolism may be associated with pseudoallergy. Extensive diagnostic measures are not indicated for an acute urticaria or a short episode of angioedema. Only when symptoms become chronic or at least intermittent, basic diagnostic measures are justified. If this procedure is unsuccessful, pseudoallergy to food components should be considered as a causative factor. In order to confirm this suspicion, patients should adhere to a low pseudoallergen diet for 3 weeks. During this period, a daily documentation of symptoms is recommended. As the underlying pathomechanism is not IgE-mediated, skin and blood tests are not useful for diagnosis. After apparent improvement or remission of symptoms, the causative role of a low pseudoallergen diet can be proven by re-esposure to foods rich in Pseudoallergens over 2 days. As food additives only play a minor role in pseudoallergic reactions, a mixture of relevant food additives can be given at one time in most patients. Patients with asthma bronchiale or a history of anaphylactoid reactions should be challenged with single food additives in increasing doses. If adverse reactions to histamine are Suspected, an oral provocation with histamine dihydrochloride is recommended. For patients with respiratory symptoms inhalant challenge tests are suggested, Double-blind, placebo-controlled food challenge is recommended if the patient suffers from gastrointestinal symptoms only and pseudoallergy is suspected.