It has been reported that liposomal formulation of a-galactosylceramide(lipo-aGC) could induce antigen specific regulatory T cells (Treg) in vivo when administered with particular antigens. We previously reported that lipo-aGC plus anti-CD40L (MR1) administration with bone marrow cells (BMCs) could induce donor specific tolerance with in vivo Treg expansion. In the current study, we investigated whether donor specific tolerance can be induced by lipo-aGC for other donor antigen-bearing grafts, such as cardiac allograft or splenocytes (SPCs).

BALB/c mice were transplanted heterotopic cardiac allograft from C57BL/6 donor mice the day after administration of lipo-aGC and/or MR1. Unlike the result of BMCs, administration of lipo-aGC could not prolong cardiac graft survival even when it was combined with MR1(figure 1). It is presumed that donor cell transfer might be indispensable to establish donor specific tolerance in this model. Therefore, BMC transfer with lipo-aGC plus MR1 after 3Gy irradiation was attempted a day before cardiac transplant. Those mice showed long term engraftment of cardiac allograft as well as that of hematopoietic cells, whereas mice treated with lipo-aGC alone or MR1 alone could not. This tolerance was restricted to the antigens of transferred BMCs because it was not established when transferred BMCs were derived from 3rd party. Instead of BMCs, we attempted transfer of SPCs from the same donor. Both cardiac graft and SPCs were rejected despite administration of lipo-aGC plus MR1(figure 2). Taken together, BMC transfer is required to induce donor specific tolerance with lipo-aGC.

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