{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:52:23Z","timestamp":1790812343947,"version":"4.1.0"},"reference-count":149,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T00:00:00Z","timestamp":1640649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008751","name":"Federal Institute for Risk Assessment","doi-asserted-by":"publisher","award":["1322-718, 1322-719, 1322-754"],"award-info":[{"award-number":["1322-718, 1322-719, 1322-754"]}],"id":[{"id":"10.13039\/501100008751","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells11010083","type":"journal-article","created":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T02:31:27Z","timestamp":1640745087000},"page":"83","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals\u2014A Systematic Review"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5483-1366","authenticated-orcid":false,"given":"Marina","family":"Aparicio-Soto","sequence":"first","affiliation":[{"name":"Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, 10589 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4938-7288","authenticated-orcid":false,"given":"Caterina","family":"Curato","sequence":"additional","affiliation":[{"name":"Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, 10589 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2395-5454","authenticated-orcid":false,"given":"Franziska","family":"Riedel","sequence":"additional","affiliation":[{"name":"Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, 10589 Berlin, Germany"},{"name":"Institute of Pharmacy, Freie Universit\u00e4t Berlin, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9655-681X","authenticated-orcid":false,"given":"Hermann-Josef","family":"Thierse","sequence":"additional","affiliation":[{"name":"Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, 10589 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Luch","sequence":"additional","affiliation":[{"name":"Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, 10589 Berlin, Germany"},{"name":"Institute of Pharmacy, Freie Universit\u00e4t Berlin, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0380-1594","authenticated-orcid":false,"given":"Katherina","family":"Siewert","sequence":"additional","affiliation":[{"name":"Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, 10589 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,28]]},"reference":[{"key":"ref_1","unstructured":"McQueen, C. 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