In vitro human T cell responses to diphencyprone

The experimental contact sensitizer Diphencyprone (DPCP) is used both for topical immunotherapy and investigation of the human immune system. Analysis of mechanisms underlying altered immune responses requires in vitro systems. We have developed a method for detecting human T cell responses to DPCP in vitro. Twenty subjects were sensitized with DPCP (30?g/cm2) and 4 weeks later, were challenged with doses from 0.48 to 3.125?g. Responses at 48h showed all 20 were allergic. Peripheral blood mononuclear cells were cultured with a range of concentrations of DPCP for 6 days and proliferation quantified (3H thymidine uptake). The subjects were exposed repeatedly to DPCP (topical immunotherapy for warts or alopecia areata) or as repeated patch test challenges. Eight subjects gave positive lymphocyte proliferation responses (LPR), maximal responses being elicited with 16 or 32?M DPCP. Positive LPR became detectable from 20 weeks after sensitization and progressively more people become responsive over time to 40 weeks. The different time courses for manifestation of allergic reactivity in skin and blood probably reflects absence of memory T cells in blood due to their recruitment to skin as resident memory T cells. This assay can now be developed for analysis of components of the immune response

Expression of PI3K signaling associated with T cells in psoriasis is inhibited by seletalisib, a PI3Kδ inhibitor, and is required for functional activity

The phosphoinositide 3-kinase (PI3K) pathway plays a key role in many cellular processes, including cell proliferation, survival, and protein synthesis, with the PI3K isoform, PI3Kδ, involved in normal T-cell development and function (Jarmin et al., 2008, Lucas et al., 2016, Vanhaesebroeck et al., 2012). Evidence to suggest that PI3K signaling might play a role in psoriasis comes from reports of increased expression of phosphorylated protein kinase B, mammalian target of rapamycin, and ribosomal protein S6 (pS6), which are downstream in the PI3K signaling pathway, in lesional psoriatic skin compared with nonlesional skin and healthy controls (Buerger et al., 2013, Madonna et al., 2012, Rosenberger et al., 2007). In addition, PI3Kδ knock-in mice, expressing a catalytically inactive form of PI3Kδ (p110δD910A/D910A), and PI3Kγ knockout mice are greatly protected from imiquimod-induced psoriasis-like skin inflammation compared with wild-type mice (Roller et al., 2012)