Changing Paradigms in Cutaneous Immunology: Adapting with Dendritic Cells

Skin testing remains an essential diagnostic tool in modern allergy practice. A signifi cant variability has been reported regarding technical procedures, interpretation of results and documentation. This review has the aim of consolidating methodological recommendations through a critical analysis on past and recent data. This will allow a better understanding on skin prick test (SPT) history; technique; (contra-) indications; interpretation of results; diagnostic pitfalls; adverse reactions; and variability factors. Skin has an important physiological role in the internal balance homeostasis and constitutes a crucial barrier against external aggressions, with well-known immunological properties. 1 It has been used by allergists for decades as an easily assessed laboratory of the immunological status of the individual.The fi rst skin testing technique was developed by Charles H. Blackley in 1865, a Manchester homeopathic physician with allergic rhinitis. He abraded a quarter-inch area of his skin with a lancet and then applied grass pollen grains. 2 The so-called scratch test was later adopted by Schloss for the diagnosis of food allergy in children. 3 Epicutaneous tests can be divided into scratch tests and prick/puncture tests. The fi rst method, proposed by Blackley 2 , implied a linear scratch without drawing blood and could either be performed fi rst, with the extract then dropped on the abraded skin, or be made through a drop of extract. 4 Although it was used extensively in the past, this technique became progressively obsolete due to patient discomfort, poor reproducibility, possible residual lesions and newer and innocuous procedures. 4 Therefore, scratch test is mentioned here for historical purposes only. It was Sir Thomas Lewis who, in 1924, fi rst applied skin prick tests (SPT). 5 Nevertheless, their generalised use in clinical practice only became a reality about 30 years ago, as a result of technique modifi cations proposed by Pepys. 6 For the purpose of this review and for easier comprehension, skin testing will be referred interchangeably as SPT, whatever device is used for its application.In 1966, Ishizaka's work on immunoglobulin E (IgE) and immediate hypersensitivity reactions 7 established the scientifi c corpus to what was done till then on a strictly empiric basis.As written by Dr Walzer in 1974, "the fact that skin testing has not turned out to be a simple and completely reliable technique does not detract from the fact that, when it is intelligently and skilfully performed, it remains the most effective diagnostic procedure in reaginic allergic disorders". 8 The reliability of skin testing and proper documentation of test results are essential in allergy practice. A recent survey to all physician members and fellows of the American College of Allergy, Asthma and Immunology practicing in the

show abstract

“…1 It has been used by allergists for decades as an easily assessed laboratory of the immunological status of the individual.…”

mentioning

confidence: 99%

Skin prick tests and allergy diagnosis

Antunes

Borrego

Romeira

et al. 2009

Allergologia et Immunopathologia

View full text Add to dashboard Cite

show abstract

“…Terminally differentiated keratinocytes form the stratum corneum, i.e., a physical barrier. The epidermis also functions as an immunological barrier by producing cytokines, antimicrobial peptides, and other mediators [1,2] and by hosting resident leukocytes, known as Langerhans cells (LCs), which represent an immature subset of the dendritic cell (DC) family of antigen presenting cells [3,4,5]. It is generally believed that LCs play dual or even counter-acting immuno-regulatory roles at this location depending on their states of maturation [6].…”

Section: Introductionmentioning

confidence: 99%

Roles for IL-1 and TNFα in dynamic behavioral responses of Langerhans cells to topical hapten application

Nishibu

Ward

Boes

et al. 2007

Journal of Dermatological Science

View full text Add to dashboard Cite

Background-To understand the behavioral biology of Langerhans cells (LCs), we recently recorded time-lapse images of LCs in the knock-in mice expressing the I-Aβ chain tagged with the enhanced green fluorescence protein (EGFP). EGFP + LCs showed relatively limited motility in the steady state, whereas topical application of dinitrofluorobenzene (DNFB) markedly augmented a unique movement of dendrites characterized by rhythmic extension and retraction, termed dSEARCH, and triggered amoeba-like lateral migration of cell bodies. Objective-To define underlying mechanisms by which hapten treatment alters LC behaviors.Methods-The I-Aβ-EGFP mice received subcutaneous (s.c.) injection of recombinant IL-1α or TNFα (50 ng/animal) and dynamic behaviors of EGFP + LCs were recorded by time-lapse confocal microscopy at several time points to measure their dSEARCH activities and lateral migration. In a different sset of experiments, IL-1 receptor antagonist (IL-1Ra) or soluble TNF receptor-2 (sTNFR2) (0.5 μg/animal) was s.c. injected into the ear skin 30 minutes before topical application of DNFB, and LC behaviors analyzed thirty hours later.Results-Local injection of IL-1α or TNFα induced significant, albeit modest, augmentation of both dSEARCH and lateral migration. Co-injection of TNFα and IL-1α further exacerbated motile activities in a synergistic manner by similar magnitudes observed after DNFB application. Conversely, DNFB-induced behavioral changes were inhibited completely by local injection of IL-1Ra or sTNFR2.Conclusion-IL-1 and TNFα serve as equally important mediators of hapten-induced alteration of LC behaviors. Motile activities of epidermal LCs are reprogrammed by selected cytokines known to be produced by keratinocytes under pathological conditions.

show abstract

“…They are potent APCs that serve as activators of skin-specific immune responses to contact sensitizers, viruses, and tumors. More recently they have been implicated in playing a major role for maintaining tolerance to damaged skin proteins (1)(2)(3)(4). As immature DCs, they can capture and process Ag at picomolar concentrations (5) but are weak stimulators of naive T cell responses.…”

mentioning

confidence: 99%

CD4 T Cell-Induced, Bid-Dependent Apoptosis of Cutaneous Dendritic Cells Regulates T Cell Expansion and Immune Responses

Pradhan¹,

Genebriera²,

Denning

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

The fate of dendritic cells (DCs) after Ag presentation may be DC subset-specific and controlled by many factors. The role of activation-induced apoptosis in regulating DC function is not clear. We investigated the fate of cutaneous DCs (cDCs), specifically Langerhans cells (LCs), and observed that they undergo apoptosis after successful Ag presentation to CD4 T cells. Caspase-specific inhibitors revealed that LC lines use a type II apoptosis pathway in response to CD4 T cells. In support of this, BH3-interacting domain (Bid) protein was present at high levels and specifically cleaved in the presence of Ag-specific T cells. Significant resistance to apoptosis by OT-2 CD4 cells was also observed for Bid knockout (KO) LCs in vitro. To test whether Bid was required to regulate LC function in vivo, we measured contact sensitization and topical immunization responses in Bid KO mice and observed markedly enhanced ear swelling and proliferation responses compared with wild-type mice. Furthermore, when Ag-pulsed Bid KO migratory cDCs were inoculated into wild-type recipients, an increase in both the rate and percentage of expanded OT-2 T cells expressing IFN-γ was observed. Thus, enhanced Ag presentation function was intrinsic to Bid KO cDCs. Therefore, Bid is an important regulator of LC viability and Ag presentation function.

show abstract

Changing Paradigms in Cutaneous Immunology: Adapting with Dendritic Cells

Cited by 82 publications

References 109 publications

Skin prick tests and allergy diagnosis

Skin prick tests and allergy diagnosis

Roles for IL-1 and TNFα in dynamic behavioral responses of Langerhans cells to topical hapten application

CD4 T Cell-Induced, Bid-Dependent Apoptosis of Cutaneous Dendritic Cells Regulates T Cell Expansion and Immune Responses

Contact Info

Product

Resources

About