Search

BACKGROUND: There is considerable interest in understanding the immunological variables that have the greatest influence on the effectiveness of sensitization by contact allergens, particularly in the context of developing new paradigms for risk assessment of novel compounds OBJECTIVES: To examine the relationship between patch test score for 3 different contact allergens and the characteristics of T-cell responses.PATIENTS/MATERIALS/METHODS: A total of 192 patients with confirmed nickel, p-phenylenediamine (PPD) or methylisothiazolinone allergy were recruited from the Contact Dermatitis Investigation Unit at Salford Royal Hospital. Severity of allergy was scored by patch testing and peripheral blood lymphocytes characterized for T cell phenotype by flow cytometry and proliferative activity by radiolabelled thymidine incorporation. Comparisons were drawn with buffy coat samples from healthy volunteers.RESULTS: Patch test positivity to nickel, PPD and MI was associated with changes in the phenotype of peripheral blood T-cells: increases in naïve cells, decreases in Treg cell frequency and the CD4+ :CD8hi ratio and increased expression of the skin homing marker CLA, particularly for those patients with a +++ patch test score.CONCLUSIONS: This increased understanding of the characteristics of the T cell responses to contact allergens may provide parameters to better measure health risks associated with skin sensitization. This article is protected by copyright. All rights reserved.

At the ESCD congress held in Manchester in 2016, a session was organized to encourage more dialogue between clinicians with expertise in skin sensitization and toxicologists seeking to provide effective risk assessment to prevent human health issues. That session focused on the remaining uncertainties regarding the induction and regulation of skin sensitization in humans, and the opportunities and challenges associated with the refinement and improvement of risk assessment methodologies. This short article, prompted by those discussions, debates what the authors regard as being among the most important and most intriguing uncertainties about skin sensitization and allergic contact dermatitis in humans, and the most significant opportunities for improving risk assessment. The aim has been to provide a basis for mapping out the areas that might benefit from a closer alignment between the relevant clinical community and toxicologists charged with the responsibility of ensuring that skin sensitization risks are understood and managed.

Summary Background Methylisothiazolinone (MI), a preservative that is commonly used in personal care products, is now recognized as an important contact allergen in both cosmetic and occupational settings. Objectives To analyse T lymphocyte responses to MI, in order to provide important information regarding the relationship between the nature of such responses and skin sensitization potency. Methods Proliferative responses to free MI and to an MI–human serum albumin (HSA) conjugate were measured according to [3H]thymidine incorporation (n = 56 donors; patch test scores of + in 20, ++ in 29, and +++ in 7). Peripheral blood mononuclear cells were cultured in the presence of MI (0.001–1 µg/ml) or MI–HSA (0.001–100 µg/ml). Proliferating CD4+ and CD8+ T lymphocytes were identified by flow cytometry with the intracellular marker Ki-67. Results For free MI, modest positive responses were recorded for 7 of 31 donors. In contrast, MI–HSA stimulated more marked responses in 17 of 31 donors. Characterization of positive proliferative responses showed variable patterns of proliferating CD4+ and CD8+ T lymphocytes from donors with the same patch test scores and similar maximal values. Conclusions MI–HSA is able to induce secondary responses in lymphocytes drawn from sensitized subjects, and provides a more effective source of antigen than free MI. Furthermore, individual donors show differential activity profiles with respect to T lymphocyte subsets.

Whereas T lymphocyte (T cell) activation is the key event in the acquisition of skin sensitization and subsequent elicitation of allergic contact dermatitis, the humoral component of immune responses to organic contact allergens has received little consideration. There is evidence that, in experimental animals, topical exposure to potent contact allergens is associated with B cell activation and proliferation, and hapten-specific antibody production. However, there is very limited evidence available for anti-hapten antibody responses being induced following topical exposure of humans to contact allergens. Nevertheless, it is important to appreciate that there are almost no negative studies in which evidence for antibody production as the result of skin sensitization has been sought and not found. That is, there is absence of evidence rather than evidence of absence. Furthermore, exposure to chemical respiratory allergens, in which the skin has been implicated as a potential route of sensitization, results in anti-hapten antibody responses. It is proposed that skin sensitization to contact allergens will normally be accompanied by antibody production. The phenomenon is worthy of investigation, as anti-hapten antibodies could potentially influence and/or regulate the induction of skin sensitization. Moreover, such antibodies may provide an informative correlate of the extent to which sensitization has been acquired.