Blockade of γc signals in combination with donor-specific transfusion induces cardiac allograft acceptance in murine models

Abstract

The γc cytokines play an important role in proliferation and survival of T cells. Blocking the γc signals can cause the activated donor-reactive T cells losing the ability to proliferate, and getting into apoptosis pathway, which contributes to induction of the peripheral tolerance. In this study, we induced the transplant tolerance through blocking the γc in combination with donor-specific transfusion (DST) in the cardiac transplantation. Following DST, on the day 2, 4 and 6, C57BL/6 recipients received anti-γc monoclonal antibodies (mAbs) injection, and those in control group were not given anti-γc mAbs. On the day 7, Balb/c cardiac allografts were transplanted. All recipients in experimental group accepted cardiac allografts over 30 days, and two of them accepted allografts without rejection until sacrifice on the 120 day. Animals only receiving DST rejected grafts within 5 days, and the mice receiving cardiac transplantation alone rejected grafts within 9 days. Our study showed that blockade of γc signaling combined with DST significantly prolonged allograft survival, which was probably associated with inhibition of antigen-specific T-cell proliferation and induction of apoptosis.

Keywords

anti-γc monoclonal antibody / donor-specific transfusion / cardiac allograft / transplant tolerance / murine model

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