title: Assessment of the usefulness of the murine cytotoxic T cell line CTLL-2 for immunotoxicity screening by transcriptomics.
abstract: A toxicogenomics approach was applied to assess the usefulness of the mouse cytotoxic T cell line CTLL-2 for in vitro immunotoxicity testing. CTLL-2 cells were exposed for 6 h to two model immunotoxic compounds: (1) the mycotoxin deoxynivalenol (DON, 1 and 2 μM), a ribotoxic stress inducer, and (2) the organotin compound tributyltin oxide (TBTO, 100 and 200 nM), an endoplasmic reticulum (ER) stress inducer. Effects on whole-genome mRNA expression were assessed by microarray analysis. The biological interpretation of the microarray data indicated that TBTO (200 nM) induced genes involved in T cell activation, ER stress, NFκB activation and apoptosis, which agreed very well with results obtained before on TBTO exposed Jurkat cells and mouse primary thymocytes. Remarkably, DON (2 μM) downregulated genes involved in T cell activation, ER stress and apoptosis, which is opposite to results obtained before for DON-exposed Jurkat cells and mouse primary thymocytes. Furthermore, the results for DON in CTLL-2 cells are also opposite to the results obtained for TBTO in CTLL-2 cells. In agreement with the lack of induction of ER stress and apoptosis, viability assays showed that CTLL-2 cells are much more resistant to the toxicity of DON than Jurkat cells and primary thymocytes. We propose that CTLL-2 cells lack the signal transduction that induces ER stress and apoptosis in response to ribotoxic stress. Based on the results for TBTO and DON, the CTLL-2 cell line does not yield an added value for immunotoxicity compared to the human Jurkat T cell line.
authors.affiliation: RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen, The Netherlands. peter.schmeits@wur.nl
authors.forename: Peter C J
authors.initials: PC
authors.lastname: Schmeits
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Volger
authors.forename: Ella T
authors.initials: ET
authors.lastname: Zandvliet
authors.forename: Henk
authors.initials: H
authors.lastname: van Loveren
authors.forename: Ad A C M
authors.initials: AA
authors.lastname: Peijnenburg
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Hendriksen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D013678:Technology, Pharmaceutical; D043922:Toxicogenetics / Q000379:methods*; D059467:Transcriptome / Q000187:drug effects*; D014220:Trialkyltin Compounds / Q000494:pharmacology; D014255:Trichothecenes / Q000494:pharmacology
chemical_list: D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D014220:Trialkyltin Compounds; D014255:Trichothecenes; C005961:bis(tri-n-butyltin)oxide; C007262:deoxynivalenol