Donor antigen is necessary for the prevention of chronic rejection in CTLA4Ig-treated murine cardiac allograft recipients

Transplantation
M H SayeghL A Turka

Abstract

Optimal activation of T cells requires two signals: antigen engagement through the T cell receptor and a costimulatory signal. Previous studies have shown that blockade of the CD28:B7 costimulatory pathway using the soluble fusion protein CTLA4Ig can prevent acute rejection of organ and tissue allografts; however, long-term engraftment has not been seen universally. This study was undertaken to define the role of donor antigen in inducing long-term allograft survival in CTLA4Ig-treated recipients. A murine cardiac allograft model was employed using BALB/c donors and C57BL/6 recipients. Additional donor antigen in the form of donor splenocytes was given at the time of transplantation. Recipients were treated with a single dose of CTLA4Ig 2 days after transplantation. We find that a single dose of CTLA4Ig prolongs cardiac allograft survival, but permanent engraftment is not observed unless the recipients receive an injection of donor-type splenocytes. Treatment of the donor cells with CTLA4Ig does not by itself prolong allograft survival, which indicates the need for systemic treatment of the recipient. Allografts from animals not receiving donor cells show classic histologic changes of chronic rejection, and most cease function ...Continue Reading

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