-specific as a result of their improved frequencies compared to controls. A skewed V- and J-gene segment usage was observed while a mechanistic association with PPD recognition remains to be defined. The study by Skazik, 2008 [101] showed by flow cytometry that 8 out of 21 PPD-specific T cell clones expressed TRBV14 (V16 in Arden DNA Methyltransferase Inhibitor web nomenclature), a segment not highlighted within the study of Oakes, 2017 [100]. 3.two.5. Characteristics of Chemical-Specific T Cell Responses in Patients Studies varied with regards to patients’ cohort composition and experimental setups. 4 case reports (13 ) incorporated only 1 to two patients with drug allergies (Girardi, 2015; Kim, 2020; Sachs, 2001; Vilchez-S chez, 2020) [108,11113]. The remaining articles included cohorts with approximately 10 and as much as 200 patch tested allergic sufferers. The proliferative response of allergic patients’ T cells to chemical compounds showed wonderful CXCR3 Agonist manufacturer variability. Generally, cells derived from sufferers with a extremely strong (+++) result in patch tests reacted far more often and possessed a larger proliferative response than cells from individuals with powerful (++) or weak (+) patch test results. A common observation on the existence of a concordance between the patient patch test result along with the patient T cell proliferative or cytokine response in vitro has been made by 4 out of 32 studies (13 ) inside the case of PPD (Bordignon, 2015; Wicks, 2019) [96,102], MCI/MI (Masjedi, 2003) [107] and parthenolide (Wahlkvist, 2008) [117]. Of note, three research didn’t confirm this concordance for PPD (Moed, 2005) [95], MI (Popple, 2016) [116] and numerous fragrances (Sieben, 2001) [105]. 3 studies (9.four ) tested the detection of chemical-specific T cells after administration of a cytokine cocktail (e.g., IL-7 + IL-12 or IL-4) towards the culture media (Kneilling, 2009; Moed, 2005; Schutte, 2019) [95,99,104]. The addition of cytokines might support the proliferative capacity of chemical-specific T cells. PPD and its derivative BB were investigated for possible T cell cross-reactivity (2/32 studies, six.3 ). For this goal, Gibson, 2015 [94] and Sieben, 2002 [80] tested PPD- and BB-specific T cell clones from allergic and healthier donors. Gibson et al. located that 75 of PPD-specific T cell clones reacted exclusively to the original antigen, while Sieben et al. discovered that many of the 25 PPD-specific T cell clones have been BB cross-reactive. Of note, BBspecific T cell responses are observed in all men and women, but PPD-specific T cells have been described only in allergic patients (Coulter, 2010; Gibson, 2015; Sieben, 2002) [80,93,94].Cells 2022, 11,13 of3.three. Monitoring Non-Antigen-Specific T Cell Activation 5 studies assessed T cell responses to chemical sensitizers (42 substances) within a non-antigen-specific manner (Supplementary Material, Table S3). Most chemicals have been fragrance agents (13), drugs (11), dyes (five) and model chemical substances (three), aside from preservatives, disinfectants and some industrial agents. Frombach, 2018 [88] assessed immunotoxic influences of chemical substances on cytokine secretion also as IL-23R/CD119, CD124 and CD44 surface expression on expanded T cells derived from mixed lymphocyte reactions containing MoDC, T cells and allogenic keratinocytes. Similarly, Clouet, 2019 [92] monitored T cell proliferation in a mixed-lymphocyte reaction with THP-1 as a DC model. The improve in co-stimulatory capacity by sensitizertreated DC reflects their prospective to support antigen-specific T cell proliferation. Hou, 2020 [89] used the Jurkat T c