T-cell receptor repertoire expression in workers with occupational asthma due to platinum salt

Raulf‐Heimsoth, Monika; Merget, R.; Hp, Rihs; Fohring, M; Liebers, Verena; Gellert, B.; Schultze‐Werninghaus, G.; Baur, Xaver

doi:10.1183/09031936.00.16587100

Cited by 19 publications

(5 citation statements)

References 27 publications

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“…Typically initial exposure is followed by a latency period (1 month to several years) before a subsequent inhalation exposure results in the development of respiratory hypersensitivity and allergic asthma Rauf-Heimsoth et al, 2000). While the weight of evidence suggests that chloroplatinate allergy is associated with IgE antibody induced sensitisation, the fact that skin prick tests apparently fail to identify all symptomatic workers (Calverley et al, 1995), suggest that other mechanisms cannot be excluded.…”

Section: Chloroplatinate Saltsmentioning

confidence: 98%

Thresholds in chemical respiratory sensitisation

et al. 2015

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There is a continuing interest in determining whether it is possible to identify thresholds for chemical allergy. Here allergic sensitisation of the respiratory tract by chemicals is considered in this context. This is an important occupational health problem, being associated with rhinitis and asthma, and in addition provides toxicologists and risk assessors with a number of challenges. In common with all forms of allergic disease chemical respiratory allergy develops in two phases. In the first (induction) phase exposure to a chemical allergen (by an appropriate route of exposure) causes immunological priming and sensitisation of the respiratory tract. The second (elicitation) phase is triggered if a sensitised subject is exposed subsequently to the same chemical allergen via inhalation. A secondary immune response will be provoked in the respiratory tract resulting in inflammation and the signs and symptoms of a respiratory hypersensitivity reaction. In this article attention has focused on the identification of threshold values during the acquisition of sensitisation. Current mechanistic understanding of allergy is such that it can be assumed that the development of sensitisation (and also the elicitation of an allergic reaction) is a threshold phenomenon; there will be levels of exposure below which sensitisation will not be acquired. That is, all immune responses, including allergic sensitisation, have threshold requirement for the availability of antigen/allergen, below which a response will fail to develop. The issue addressed here is whether there are methods available or clinical/epidemiological data that permit the identification of such thresholds. This document reviews briefly relevant human studies of occupational asthma, and experimental models that have been developed (or are being developed) for the identification and characterisation of chemical respiratory allergens. The main conclusion drawn is that although there is evidence that the acquisition of sensitisation to chemical respiratory allergens is a dose-related phenomenon, and that thresholds exist, it is frequently difficult to define accurate numerical values for threshold exposure levels. Nevertheless, based on occupational exposure data it may sometimes be possible to derive levels of exposure in the workplace, which are safe. An additional observation is the lack currently of suitable experimental methods for both routine hazard characterisation and the measurement of thresholds, and that such methods are still some way off. Given the current trajectory of toxicology, and the move towards the use of non-animal in vitro and/or in silico) methods, there is a need to consider the development of alternative approaches for the identification and characterisation of respiratory sensitisation hazards, and for risk assessment.

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Section: Chloroplatinate Saltsmentioning

confidence: 98%

Thresholds in chemical respiratory sensitisation

et al. 2015

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“…Only after stimulation with the allergen Chi t 1–9 (5 µg/ml) for several days [1], or after stimulation for 24 h with IL-4, did the importance of Vβ8a become visible. Investigations in platinum salt-allergic subjects [22, 23]also revealed a time- and dose-dependent increase in Vβ8a-positive cells due to platinum salt stimulation. In addition, Vβ5.3-, Vβ6.7-, Vβ20- and Vβ21.3-positive cells also expanded under these stimulation conditions.…”

Section: Discussionmentioning

confidence: 99%

Does IL-4 Play a Role in the Expansion of Vβ8a T Cell Receptor-Bearing Cells?

Liebers

Gellert²,

Raulf‐Heimsoth³

et al. 2001

Int Arch Allergy Immunol

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Background: Peripheral blood mononuclear cells (PBMC) of subjects allergic to the insect-derived allergen Chi t 1–9 are characterized by an allergen-induced pronounced proliferation and increased expression of activation markers (CD25, HLA-DR, CD23). T cell lines showed an elevated percentage of Vβ8a-positive cells following stimulation by Chi t 1–9. Objective: The aim of the present study was to investigate whether Vβ8a dominance plays an important role in PBMC short-term cultures (24 h) as well. The role of exogenous added cytokines, especially IL-4, has been determined. Methods: The T cell receptor repertoire was measured with 16 monoclonal antibodies to epitopes on the variable region of the β chain by flow cytometry. Patients allergic to Chi t 1–9 were compared to nonallergic subjects as well as to subjects with other occupational allergies. In addition, cytokines were determined intracellulary by flow cytometry. Studies were performed with PBMC cultured for 24 h. Results: After cultivation for 24 h without or with different stimuli (cytokines, allergen, phytohaemagglutinin), changes in the T cell receptor profile and the cytokine profile were measurable compared to the baseline value (without cultivation). Stimulation with IL-4 revealed increased percentages of Vβ8a-expressing cells in Chi t 1–9-sensitized patients. This IL-4-induced Vβ8a increase did not occur in PBMC from the two control subject groups (non-allergic and allergic to other allergens than Chi t 1–9). Conclusion: In conclusion, the dominance of certain T cell receptor types seems to arise due to the exposure to specific allergens and cytokine production. Some T cell receptors are often affected, for example Vβ8a, whereas others only show minor variations. Vβ8a expression obviously plays an important role in Chi t 1–9 allergy.

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“…Darüber hinaus zeigten Untersuchungen im Basisprofil platinsalzallergischer Patienten, dass der Prozentsatz an T-Zellen, die die TCR Vá2a, Vâ5.2, Vâ11 und Vâ21 tragen, signifikant höher ist, als in einem nicht-exponierten Kontrollkollektiv [30] (Abb. 2).…”

Section: Tcr Und Erkrankungunclassified

T-Cell Receptor and Allergy - A Survey

Liebers

Raulf‐Heimsoth²

2001

Pneumologie

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Das Immunsystem stellt ein hochentwickeltes Abwehrsystem der Wirbeltiere dar, an dem viele verschiedene Zelltypen beteiligt sind. Eine entscheidende Rolle spielen dabei die Lymphozyten mit ihren Antigenrezeptoren. Sie sind für die Spezifität der Reaktionen verantwortlich. B-, T-und NK-Zellen sind die wesentlichen Lymphozytenpopulationen, die unterschieden werden. T-Zellen haben wichtige regulatorische Funktionen. Sie unterstützen als T-Helfer-Zellen bestimmte Immunantworten, z. B. die Immunglobulinproduktion. Die zytotoxischen T-Zellen sind dagegen in direkte Effektorfunktionen involviert, z. B. in die Lyse Virus-infizierter Zellen.

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T-cell receptor repertoire expression in workers with occupational asthma due to platinum salt

Cited by 19 publications

References 27 publications

Thresholds in chemical respiratory sensitisation

Thresholds in chemical respiratory sensitisation

Does IL-4 Play a Role in the Expansion of Vβ8a T Cell Receptor-Bearing Cells?

T-Cell Receptor and Allergy - A Survey

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