Chemical-Specific T Cell Tests Aim to Bridge a Gap in Skin Sensitization Evaluation

Area of Science:

• Immunology
• Toxicology
• Dermatology

Background:

• T cell activation is a critical step in the adverse outcome pathway (AOP) of skin sensitization.
• Validated new approach methodologies (NAMs) for assessing T cell activation are currently lacking, hindering regulatory identification of potent T cell activators like nickel.
• T cell responses are crucial for understanding chemical cross-reactivity and allergies, especially in complex exposure scenarios involving skin injury or co-exposures.

Purpose of the Study:

• To review and summarize existing solutions and strategies for confirming in vitro T cell activation signals.
• To highlight the challenges associated with current T cell testing methods, including chemical toxicity and low throughput.
• To advocate for the broader application and standardization of T cell tests in regulatory risk assessment for skin sensitizers.

Main Methods:

• Summarization of various experimental T cell assays using primary human CD4+ and CD8+ T cells.
• Discussion of priming, lymphocyte proliferation tests, and activation-induced marker (AIM) assays.
• Analysis of challenges such as chemical-mediated toxicity and epitope generation.

Main Results:

• Several experimental T cell assays are available, utilizing human T cells from blood.
• Key challenges identified include chemical toxicity, inefficient epitope generation, and low assay throughput.
• Strategies to confirm in vitro T cell signals are discussed.

Conclusions:

• Standardization and broader application of T cell tests are essential for defining chemical applicability domains.
• Strengthening the role of T cell tests in regulatory risk assessment is crucial for chemical safety.
• Addressing current limitations will improve the identification of skin sensitizers and allergens.