Increased Expressions of Programmed Death Ligand 1 and Galectin 9 in Transplant Recipients Who Achieved Tolerance After Immunosuppression Withdrawal.

Programmed cell death protein 1 (PD-1)/its ligand PD-L1, concomitant with T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3)/its ligand galectin 9 (Gal-9) and the forkhead box protein P3 (Foxp3) might be involved in tolerance after liver transplantation (LT). Liver biopsies from 38 tolerant, 19 nontolerant (including 16 samples that triggered reintroduction of immunosuppression (IS) and 19 samples after IS reintroduction) and 38 control LT patients were studied. The expressions of PD-1, PD-L1, Gal-9, and Foxp3 were determined by immunohistochemical and immunofluorescence (IF) staining. The success period of IS withdrawal was calculated using Kaplan-Meier analysis. Tolerant and control patients exhibited higher PD-L1, higher Gal-9, and higher Foxp3 levels than nontolerant patients at the moment of triggering IS reintroduction. High expression of PD-L1 and Gal-9 was associated with prolonged success of tolerance (83.3% vs. 36.7%, p<0.01; 73.1% vs. 42.9%, p=0.03). A strong correlation between PD-L1 and Gal-9 expression levels was detected (Spearman r=0.73, p=<0.0001) and IF demonstrated colocalization of PD-L1 and Gal-9 in the cytoplasm of hepatocytes. In conclusion, the present study demonstrated that an increased expression of PD-L1 and Gal-9 was associated with sustained tolerance after IS withdrawal in pediatric liver transplantation.