Performance of a novel in vitro assay for skin sensitization based on activation of T lymphocytes

Hou, Fanfan; Xing, Chao; Li, Bin; Cheng, Juan; Chen, Wei

doi:10.14573/altex.2001312

Cited by 4 publications

(8 citation statements)

References 57 publications

(98 reference statements)

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“…In total, we reviewed 37 articles and referred to them here with first author and publication year in addition to the bibliography numbering system. Among these, 32 publications described antigen-specific T cell activation (17 from PubMed, 15 from Scopus) and the others non-TCR-mediated T cell activation (2 from PubMed, 3 from Scopus) [ 88 , 89 , 90 , 91 , 92 ].…”

Section: Resultsmentioning

confidence: 99%

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In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals—A Systematic Review

Aparicio‐Soto

Curato

Riedel

et al. 2021

Cells

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Background: Chemical allergies are T cell-mediated diseases that often manifest in the skin as allergic contact dermatitis (ACD). To prevent ACD on a public health scale and avoid elicitation reactions at the individual patient level, predictive and diagnostic tests, respectively, are indispensable. Currently, there is no validated in vitro T cell assay available. The main bottlenecks concern the inefficient generation of T cell epitopes and the detection of rare antigen-specific T cells. Methods: Here, we systematically review original experimental research papers describing T cell activation to chemical skin sensitizers. We focus our search on studies published in the PubMed and Scopus databases on non-metallic allergens in the last 20 years. Results: We identified 37 papers, among them 32 (86%) describing antigen-specific human T cell activation to 31 different chemical allergens. The remaining studies measured the general effects of chemical allergens on T cell function (five studies, 14%). Most antigen-specific studies used peripheral blood mononuclear cells (PBMC) as antigen-presenting cells (APC, 75%) and interrogated the blood T cell pool (91%). Depending on the individual chemical properties, T cell epitopes were generated either by direct administration into the culture medium (72%), separate modification of autologous APC (29%) or by use of hapten-modified model proteins (13%). Read-outs were mainly based on proliferation (91%), often combined with cytokine secretion (53%). The analysis of T cell clones offers additional opportunities to elucidate the mechanisms of epitope formation and cross-reactivity (13%). The best researched allergen was p-phenylenediamine (PPD, 12 studies, 38%). For this and some other allergens, stronger immune responses were observed in some allergic patients (15/31 chemicals, 48%), illustrating the in vivo relevance of the identified T cells while detection limits remain challenging in many cases. Interpretation: Our results illustrate current hardships and possible solutions to monitoring T cell responses to individual chemical skin sensitizers. The provided data can guide the further development of T cell assays to unfold their full predictive and diagnostic potential, including cross-reactivity assessments.

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Section: Resultsmentioning

confidence: 99%

“…Hou, 2020 [ 89 ] used the Jurkat T cell line to measure increased CD69 expression upon exposure to 24 non-metallic sensitizing chemicals compared to control substances ( Supplementary Material, Table S3 ). This approach is reminiscent of systems that assess activation of keratinocytes or DC by sensitizing chemicals [ 121 , 122 ].…”

Section: Resultsmentioning

confidence: 99%

In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals—A Systematic Review

Aparicio‐Soto

Curato

Riedel

et al. 2021

Cells

View full text Add to dashboard Cite

show abstract

“…Agents that are unstable in the atmosphere or water were not assessed to avoid inaccuracies in the evaluations, although it would be better to have a greater number of test chemicals evaluated for the further validation. In addition, evaluation indices other than IL-2 mentioned above will be used to complement the skin sensitization evaluation data related to KE4 by combining the test system with the test system using CD69 as an index, as this has already been examined ( 11 ), and/or the THP-1 cell and CD4 + T-lymphocyte co-culture system ( 24 , 25 ).…”

Section: Discussionmentioning

confidence: 99%

“…All chemicals used in the present study were obtained from Sigma-Aldrich (Merck KGaA) or Tokyo Chemical Industry. The concentrations of chemicals used for cell viability studies were determined by referring to the exposure experiments on Jurkat cells ( 11 , 16 ). Saline was used as a solvent for NiSO 4 , glyoxal and lactic acid, and DMSO was used as a solvent for the other chemicals.…”

Section: Methodsmentioning

confidence: 99%

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Evaluation of skin sensitization based on interleukin‑2 promoter activation in Jurkat cells

et al. 2021

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Proof of concept testing of a positive reference material for in vivo and in vitro sensitization testing of medical devices

Okamoto,

Fukui,

Kobayashi

et al. 2024

J Biomed Mater Res

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In vivo skin sensitization tests are required to evaluate the biological safety of medical devices in contact with living organisms to provide safe medical care to patients. Negative and positive reference materials have been developed for biological tests of cytotoxicity, implantation, hemolysis, and in vitro skin irritation. However, skin sensitization tests are lacking. In this study, polyurethane sheets containing 1 wt/wt % 2,4‐dinitrochlorobenzene (DNCB‐PU) were developed and evaluated as a positive reference material for skin sensitization tests. DNCB‐PU sheet extracts prepared with sesame oil elicited positive sensitization responses for in vivo sensitization potential in the guinea pig maximization test and the local lymph node assay. Furthermore, DNCB‐PU sheet extracts prepared with water and acetonitrile, 10% fetal bovine serum‐containing medium, or sesame oil elicited positive sensitization responses as alternatives to animal testing based on the amino acid derivative reactivity assay, human cell line activation test, and epidermal sensitization assay, respectively. These data suggest that the DNCB‐PU sheet is an effective extractable positive reference material for in vivo and in vitro skin sensitization testing in medical devices. The formulation of this reference material will lead to the development of safer medical devices that contribute to patient safety.

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Performance of a novel in vitro assay for skin sensitization based on activation of T lymphocytes

Cited by 4 publications

References 57 publications

In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals—A Systematic Review

In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals—A Systematic Review

Evaluation of skin sensitization based on interleukin‑2 promoter activation in Jurkat cells

Proof of concept testing of a positive reference material for in vivo and in vitro sensitization testing of medical devices

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