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Human γ/δ T-cell proliferation and IFN-γ production induced by hexamethylene diisocyanate  Adam V Wisnewski, PhD, Christina A Herrick, MD, PhD, Qing Liu,

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Presentation on theme: "Human γ/δ T-cell proliferation and IFN-γ production induced by hexamethylene diisocyanate  Adam V Wisnewski, PhD, Christina A Herrick, MD, PhD, Qing Liu,"— Presentation transcript:

1 Human γ/δ T-cell proliferation and IFN-γ production induced by hexamethylene diisocyanate 
Adam V Wisnewski, PhD, Christina A Herrick, MD, PhD, Qing Liu, PhD, Liang Chen, PhD, Kim Bottomly, PhD, Carrie A Redlich, MD, MPH  Journal of Allergy and Clinical Immunology  Volume 112, Issue 3, Pages (September 2003) DOI: /S (03)

2 FIG 1 HDI induces proliferation of specific CD3+ cells in vitro. Human T-cell lines from 2 representative HDI-exposed (E037 and E078) and HDI-unexposed subjects (U903 and U838) were stimulated for 2 weeks with media (Med), albumin (Alb), HDI-conjugated albumin (HDI-Alb), epithelial cell antigen (Epit), HDI-exposed epithelial cell antigen (HDI-Epit), and tetanus toxoid (TT). Flow cytometry dot plots gated on live cells are shown for CD3 vs CD8 (A) and CD4 vs CD8, gated on CD3 (B). CD4−CD8dim and CD4−CD8− T cells selectively induced by HDI are circled. Journal of Allergy and Clinical Immunology  , DOI: ( /S (03) )

3 FIG 2 HDI stimulates proliferation of peripheral blood γ/δ T cells from exposed workers. PBMCs from HDI-exposed workers and nonexposed control subjects were stimulated with antigen for 2 to 3 weeks followed by flow cytometry staining for γ/δ T-cell receptor, as described in the Methods section. Stimuli included media (Med), albumin (Alb), HDI-conjugated albumin (HDI-Alb), epithelial cell antigen (Epit), HDI-exposed epithelial cell antigen (HDI-Epit), and tetanus toxoid (TT). Journal of Allergy and Clinical Immunology  , DOI: ( /S (03) )

4 FIG 3 HDI-driven γ/δ T cells use Vγ9/Vδ2 genes. T-cell lines from subject E801 and E037 driven with HDI-conjugated albumin (HDI-Alb) and HDI-exposed epithelial cell antigen (HDI-Epit) were 3-color–stained for γ/δ TCR, Vγ9, and Vδ2. Flow cytometry dot plot analysis of Vγ9 vs Vδ2 cell surface expression by HDI-driven T-cell lines is gated on γ/δ+ T cells. Journal of Allergy and Clinical Immunology  , DOI: ( /S (03) )

5 FIG 4 HDI-driven γ/δ T cells are associated with TH1-like cytokine profiles. Percentage of γ/δ T cells in HDI-albumin–stimulated cultures compared with control T cell lines is shown in top bar graph for 3 HDI-exposed workers. Lower 3 graphs show indicated cytokine levels (pg/mL) in culture supernatants at 2 weeks as detected by ELISA. In all 4 panels, stimuli were media (open bars), albumin (striped bars), and HDI-albumin (black bars). ∗Statistically significant difference (P < .005) compared with control cultures. Journal of Allergy and Clinical Immunology  , DOI: ( /S (03) )

6 FIG 5 HDI-driven γ/δ T cells produce IFN-γ. HDI-albumin–driven T-cell line from representative HDI-exposed worker (E801) were harvested after 2 weeks of in vitro stimulation and incubated with monensin 8 hours before intracellular cytokine analysis. Flow cytometry dot plots for γ/δ TCR vs cytokines, IFN-γ, IL-13 and IL-5 (right), or control mAb staining (left) are gated on CD3+ cells. Journal of Allergy and Clinical Immunology  , DOI: ( /S (03) )

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