CD70-silenced dendritic cells induce immune tolerance in immune thrombocytopenia patients

摘要

The hyper-response of dendritic cell (DC) is believed to participate in the pathogenesis of immune thrombocytopenia (ITP). The CD70 expression on the surface of DCs that takes part in the CD27-CD70 costimulation pathway is an important element of DC 'licensing', which may initiate a series of autoreactive immune responses. To elucidate the roles CD70 molecules play in the DCs of ITP patients, we first stimulated the CD70 molecules on the DCs of ITP patients and normal controls, and found that the stimulated DCs from ITP patients exhibited higher ability to induce CD4(+)CD25(-) T lymphocytes proliferation, while lowering the ability of the induction of regulatory T cells (Tregs) from CD4(+)CD25(-) T lymphocytes. Meanwhile, higher IFN-gamma and lower IL-10 levels were found in the co-culture system of stimulated DCs and CD4(+)CD25(-) T cells. We then silenced the CD70 genes on the induced DCs of ITP patients and normal controls by siRNA, and confirmed our suggestion that the silence of CD70 expression on the surface of DCs from ITP patients would decrease the CD4(+)CD25(-) T lymphocytes proliferation and Tregs differentiation, simultaneously inducing higher IL-10 and lower IFN-gamma levels. Thus, the interference with the CD27-CD70 costimulatory pathway might lead to the alleviation of the consequent immune reactions, polarisation of Th2, induction of immune tolerance as well as shed new light on treatment of autoimmune diseases.