Porcine donor leucocyte infusion leads to long-term chimerism in non-immunosuppressed primates
Introduction Infusion of donor leucocytes prior to organ transplantation (TX) is known to increase organ survival time in animal models and clinical Tx and has even been shown to be able to induce tolerance. We extended this concept to a pig-to-primate organ transplantation model.
Materials and methods Baboons underwent sequential α-Gal column adsorptions (CA), followed by donor kidney perfusion (DKP). Prior to infusion of donor cells, animals received cyclophosphamide and complement blockade. No additional immunosuppression was given. Donor cells were prepared from spleens and purified by gradient centrifugation. Recipients received 3 × 1010 donor cells each. Subsequently the animals underwent thymus or orthohotopic lung transplantation. Long-term analysis was performed for chimerism, mAb levels, serum toxicity and PERV infection.
Results CA, combined with DKP dropped Ab levels to almost naught. Adsorbtion and complement blockade significantly reduced serum toxicity. Cell infusion had no detrimental effects on recipients. No PERV infection was detected at any time. Chimerism was detected up to 4 days post cell infusion by flow cytometry in the peripheral blood, after which it dropped below level of detection. PCR showed chimerism in skin, lymph node, muscle and lung up to 530 days post cell infusion. PCR showed chimerism at the site of donor thymic implantation at the time of explantation. Imunohistochemistry showed porcine cells up to 530 days post cell infusion.
Conclusions Infusion of ultra-high number of donor cells leads to long-term micro chimerism in non-immunosuppressed primates. We are currently examining the immunomodulatory effect of our regimen.