Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, 10589 Berlin, Germany.
Institute of Pharmacy, Freie Universität Berlin, 14195 Berlin, Germany.
Cells. 2021 Dec 28;11(1):83. doi: 10.3390/cells11010083.
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.
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.
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 -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.
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.
化学过敏是 T 细胞介导的疾病，常表现为过敏性接触性皮炎（ACD）。为了在公共卫生层面预防 ACD，并避免个体患者的激发反应，预测和诊断测试分别是不可或缺的。目前，还没有经过验证的体外 T 细胞检测方法。主要的瓶颈在于 T 细胞表位的生成效率低下，以及稀有抗原特异性 T 细胞的检测。
在这里，我们系统地回顾了描述化学皮肤致敏原引起 T 细胞激活的原始实验研究论文。我们的搜索重点是在过去 20 年中在 PubMed 和 Scopus 数据库中发表的关于非金属过敏原的研究。
我们确定了 37 篇论文，其中 32 篇（86%）描述了 31 种不同化学过敏原引起的抗原特异性人 T 细胞激活。其余的研究测量了化学过敏原对 T 细胞功能的一般影响（5 项研究，14%）。大多数抗原特异性研究使用外周血单核细胞（PBMC）作为抗原呈递细胞（APC，75%），并检测血液 T 细胞库（91%）。根据单个化学性质，T 细胞表位通过直接在培养基中给药（72%）、分别修饰自体 APC（29%）或使用半抗原修饰的模型蛋白（13%）生成。读出主要基于增殖（91%），通常与细胞因子分泌（53%）相结合。T 细胞克隆的分析提供了额外的机会来阐明表位形成和交叉反应的机制（13%）。研究最多的过敏原是 -苯二胺（PPD，12 项研究，38%）。对于这种和其他一些过敏原，一些过敏患者观察到更强的免疫反应（31 种化学物质中的 15 种，48%），这说明了所鉴定的 T 细胞在体内的相关性，同时在许多情况下，检测限仍然具有挑战性。
我们的结果说明了监测个体化学皮肤致敏原引起的 T 细胞反应的当前困难和可能的解决方案。提供的数据可以指导进一步开发 T 细胞检测方法，以充分发挥其预测和诊断潜力，包括交叉反应评估。
