PD-L1 blockade ameliorates suppression of tolerogenic dendritic cells on immunoactivity of T lymphocytes in spleen of zymosan-injured mice / 临床与实验病理学杂志

ABSTRACT

Purpose To investigate the effect of tolerogenic dendritic cells ( DC) on T lymphocytes in the spleen during the develop-ment of zymosan-induced sepsis in mice, and to explore whether PD-L1 blockade could alleviate the immunosuppressive effect of tolero-genic DC on T lymphocytes. Methods Mice sepsis model was established by intraperitoneal injection of zymosan. Splenic DC and T lymphocytes were isolated respectively by using anti-CD11c and anti-CD3 magnetic beads. The expressions of PD-L1, PD-1 and PIR-B on splenic DC were measured, and IL-12 and IL-10 secreted from DC were determined. Mitogen-induced T lymphocyte proliferation and IL-2 secretion were assessed. Anti- PD-L1 antibody was added into mixed culture of tolerogenic DCs with normal Tcells. T cell proliferation and IL-2, IL-12 and IL-10 concentrations in the supernatant of mixed culture were determined. Results At 5 days and 12 days after zymosan injection, the expressions of PD-L1, PD-1 and PIR-B on splenic DC increased greatly, secretion of IL-12p70 re-duced and that of IL-12p40 and IL-10 augmented in DC, which were associated with decrease of T cells proliferation and IL-2 secre-tion. Administrating anti-PD-L1 antibody into the mixed culture of tolerogenic DC and Tcell could alleviate the suppression of DC on T lymphocyte proliferation and secretion of IL-2, and ameliorate the ability of DC secreting IL-12 and IL-10 as well. Conclusions At late stage of zymosan-induced sepsis, the formation of splenic tolerogenic DC resulted in immunosuppression of T lymphocytes. Anti-PD-L1 antibody could improve the immunoactivity of DC and T lymphocyte through intervening PD-L1/PD-1 pathway.