Cargando…

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

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....

Descripción completa

Detalles Bibliográficos
Autores principales: Aparicio-Soto, Marina, Curato, Caterina, Riedel, Franziska, Thierse, Hermann-Josef, Luch, Andreas, Siewert, Katherina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750770/
https://www.ncbi.nlm.nih.gov/pubmed/35011644
http://dx.doi.org/10.3390/cells11010083
_version_ 1784631536225615872
author Aparicio-Soto, Marina
Curato, Caterina
Riedel, Franziska
Thierse, Hermann-Josef
Luch, Andreas
Siewert, Katherina
author_facet Aparicio-Soto, Marina
Curato, Caterina
Riedel, Franziska
Thierse, Hermann-Josef
Luch, Andreas
Siewert, Katherina
author_sort Aparicio-Soto, Marina
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8750770
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-87507702022-01-12 In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals—A Systematic Review Aparicio-Soto, Marina Curato, Caterina Riedel, Franziska Thierse, Hermann-Josef Luch, Andreas Siewert, Katherina Cells Review 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. MDPI 2021-12-28 /pmc/articles/PMC8750770/ /pubmed/35011644 http://dx.doi.org/10.3390/cells11010083 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Aparicio-Soto, Marina
Curato, Caterina
Riedel, Franziska
Thierse, Hermann-Josef
Luch, Andreas
Siewert, Katherina
In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals—A Systematic Review
title In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals—A Systematic Review
title_full In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals—A Systematic Review
title_fullStr In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals—A Systematic Review
title_full_unstemmed In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals—A Systematic Review
title_short In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals—A Systematic Review
title_sort in vitro monitoring of human t cell responses to skin sensitizing chemicals—a systematic review
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750770/
https://www.ncbi.nlm.nih.gov/pubmed/35011644
http://dx.doi.org/10.3390/cells11010083
work_keys_str_mv AT apariciosotomarina invitromonitoringofhumantcellresponsestoskinsensitizingchemicalsasystematicreview
AT curatocaterina invitromonitoringofhumantcellresponsestoskinsensitizingchemicalsasystematicreview
AT riedelfranziska invitromonitoringofhumantcellresponsestoskinsensitizingchemicalsasystematicreview
AT thiersehermannjosef invitromonitoringofhumantcellresponsestoskinsensitizingchemicalsasystematicreview
AT luchandreas invitromonitoringofhumantcellresponsestoskinsensitizingchemicalsasystematicreview
AT siewertkatherina invitromonitoringofhumantcellresponsestoskinsensitizingchemicalsasystematicreview