Figure 2.

TGF-β inhibits both antitumor cytotoxicity and antigenic activation of human Vγ9Vδ2 T cells. PBL-derived Vγ9Vδ2 T cells were pretreated, or not, with TGF-β (10 ng/mL) for 72 h. (A) Cytotoxic reactivities of TGF-β-treated (closed symbols) vs untreated (open symbols) human Vγ9Vδ2 T lymphocytes against human tumor cells (Raji, left; GBM-1, right) using ⁵¹Cr-release assays. Target cells have been sensitized, or not, with zoledronate (Zol) at 5 μM and 50 µM. Results are expressed as % of cytotoxicity (mean ± SD). (B) and (C) Frequency of CD107a⁺ cells among TGF-β-treated (closed symbols) vs untreated (open symbols) TCR Vδ2⁺ lymphocytes (%) after stimulation with increasing concentrations of anti-CD3 mAb (OKT3) (B) or zoledronate (Zol)-treated, or not, human SKOV3 (left) or GBM-1 (right) tumor cells (C). E/T ratio 1/1. Positive control: BrHPP (3 µM). n≥5 for (B) and (C), mean ± SD. (D) and (E) Expression levels of activation-related molecules (TCR, NKG2A, NKG2D, ICAM1, TRAIL, FASL) (D) and cytolytic (Perforin, Granzyme B) molecules (E) by TGF-β-treated (closed symbols) vs untreated (open symbols) TCR Vδ2⁺ lymphocytes measured by flow cytometry. n=8 for (D) and (E). RFI, Relative Fluorescence Intensity. Mann-Whitney *p<0.05; **p<0.01; ****p<0.001. ns, not significant.