Chemical-Specific T Cell Tests Aim to Bridge a Gap in Skin Sensitization Evaluation
T cell activation is the final key event (KE4) in the adverse outcome pathway (AOP) of skin sensitization. However, validated new approach methodologies (NAMs) for evaluating this step are missing. Accordingly, chemicals that activate an unusually high frequency of T cells, as does the most prevalen...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-11-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/12/11/802 |
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| author | Nele Fritsch Marina Aparicio-Soto Caterina Curato Franziska Riedel Hermann-Josef Thierse Andreas Luch Katherina Siewert |
| author_facet | Nele Fritsch Marina Aparicio-Soto Caterina Curato Franziska Riedel Hermann-Josef Thierse Andreas Luch Katherina Siewert |
| author_sort | Nele Fritsch |
| collection | DOAJ |
| description | T cell activation is the final key event (KE4) in the adverse outcome pathway (AOP) of skin sensitization. However, validated new approach methodologies (NAMs) for evaluating this step are missing. Accordingly, chemicals that activate an unusually high frequency of T cells, as does the most prevalent metal allergen nickel, are not yet identified in a regulatory context. T cell reactivity to chemical sensitizers might be especially relevant in real-life scenarios, where skin injury, co-exposure to irritants in chemical mixtures, or infections may trigger the heterologous innate immune stimulation necessary to induce adaptive T cell responses. Additionally, cross-reactivity, which underlies cross-allergies, can only be assessed by T cell tests. To date, several experimental T cell tests are available that use primary naïve and memory CD4+ and CD8+ T cells from human blood. These include priming and lymphocyte proliferation tests and, most recently, activation-induced marker (AIM) assays. All approaches are challenged by chemical-mediated toxicity, inefficient or unknown generation of T cell epitopes, and a low throughput. Here, we summarize solutions and strategies to confirm in vitro T cell signals. Broader application and standardization are necessary to possibly define chemical applicability domains and to strengthen the role of T cell tests in regulatory risk assessment. |
| format | Article |
| id | doaj-art-17351e7e871d4c7ca170bf7d74bccce1 |
| institution | Kabale University |
| issn | 2305-6304 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj-art-17351e7e871d4c7ca170bf7d74bccce12024-11-26T18:23:51ZengMDPI AGToxics2305-63042024-11-01121180210.3390/toxics12110802Chemical-Specific T Cell Tests Aim to Bridge a Gap in Skin Sensitization EvaluationNele Fritsch0Marina Aparicio-Soto1Caterina Curato2Franziska Riedel3Hermann-Josef Thierse4Andreas Luch5Katherina Siewert6German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Dermatotoxicology Study Centre, 10589 Berlin, GermanyGerman Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Dermatotoxicology Study Centre, 10589 Berlin, GermanyGerman Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Dermatotoxicology Study Centre, 10589 Berlin, GermanyGerman Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Dermatotoxicology Study Centre, 10589 Berlin, GermanyGerman Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Dermatotoxicology Study Centre, 10589 Berlin, GermanyGerman Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Dermatotoxicology Study Centre, 10589 Berlin, GermanyGerman Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Dermatotoxicology Study Centre, 10589 Berlin, GermanyT cell activation is the final key event (KE4) in the adverse outcome pathway (AOP) of skin sensitization. However, validated new approach methodologies (NAMs) for evaluating this step are missing. Accordingly, chemicals that activate an unusually high frequency of T cells, as does the most prevalent metal allergen nickel, are not yet identified in a regulatory context. T cell reactivity to chemical sensitizers might be especially relevant in real-life scenarios, where skin injury, co-exposure to irritants in chemical mixtures, or infections may trigger the heterologous innate immune stimulation necessary to induce adaptive T cell responses. Additionally, cross-reactivity, which underlies cross-allergies, can only be assessed by T cell tests. To date, several experimental T cell tests are available that use primary naïve and memory CD4+ and CD8+ T cells from human blood. These include priming and lymphocyte proliferation tests and, most recently, activation-induced marker (AIM) assays. All approaches are challenged by chemical-mediated toxicity, inefficient or unknown generation of T cell epitopes, and a low throughput. Here, we summarize solutions and strategies to confirm in vitro T cell signals. Broader application and standardization are necessary to possibly define chemical applicability domains and to strengthen the role of T cell tests in regulatory risk assessment.https://www.mdpi.com/2305-6304/12/11/802adverse outcome pathwayallergic contact dermatitischemical-induced T cell epitopescontact allergensin vitro T cell testkey events |
| spellingShingle | Nele Fritsch Marina Aparicio-Soto Caterina Curato Franziska Riedel Hermann-Josef Thierse Andreas Luch Katherina Siewert Chemical-Specific T Cell Tests Aim to Bridge a Gap in Skin Sensitization Evaluation Toxics adverse outcome pathway allergic contact dermatitis chemical-induced T cell epitopes contact allergens in vitro T cell test key events |
| title | Chemical-Specific T Cell Tests Aim to Bridge a Gap in Skin Sensitization Evaluation |
| title_full | Chemical-Specific T Cell Tests Aim to Bridge a Gap in Skin Sensitization Evaluation |
| title_fullStr | Chemical-Specific T Cell Tests Aim to Bridge a Gap in Skin Sensitization Evaluation |
| title_full_unstemmed | Chemical-Specific T Cell Tests Aim to Bridge a Gap in Skin Sensitization Evaluation |
| title_short | Chemical-Specific T Cell Tests Aim to Bridge a Gap in Skin Sensitization Evaluation |
| title_sort | chemical specific t cell tests aim to bridge a gap in skin sensitization evaluation |
| topic | adverse outcome pathway allergic contact dermatitis chemical-induced T cell epitopes contact allergens in vitro T cell test key events |
| url | https://www.mdpi.com/2305-6304/12/11/802 |
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