Th17-Derived Th1 Cells Resemble Progenitor Exhausted CD4+ T Cells and Exhibit Augmented Anti-tumor Efficacy

Th17 cells exhibit superior stemness and differentiation capabilities. Under specific conditions, they can be induced to differentiate into various subtypes. Here we reported that Th17-derived Th1 cells, when compared to conventional Th1 and Th17 cells, manifest less exhausted phenotype and enhanced anti-tumor activity. Naïve T cells were isolated from splenocytes of C57BL/6 mice and cultured with plated-bound anti-CD3 (5 mg/mL) and soluble anti-CD28 (1 mg/mL) for 3 days under different conditions (Th1 for 10 ng/mL IL-12, 5 mg/mL anti-IL-4; Th17 for 1 ng/mL TGF-b, 20 ng/mL IL-6, 10 ng/mL IL-1b, 20 mg/mL anti-IFN-g, 5 mg/mL anti-IL-12 and 5 mg/ml anti-IL-4). Then T cells were collected and further cultured for 2 days with cytokines only. On day 5, cells were cultured with IL-2 (100 U/mL) for 2 more days. Then Th cells were re-stimulated with soluble anti-CD3 (0.05ug/mL), anti-CD28 (0.05ug/mL), IL2 (100U/mL) on day 7 in the presence of Th1 or Th17 conditions for 3 days. Total RNA of T cells was prepared using RNAex Pro RNA Reagent (AG, AG21102) on day 10 for RNAseq.