Active role of chimerism in transplantation tolerance induced by antilymphocyte serum, sirolimus, and bone-marrow-cell infusion

Transplantation
Akira KanamotoTakashi Maki

Abstract

A regimen consisting of antilymphocyte serum (ALS), sirolimus, and donor bone-marrow-cell (BMC) infusion induces indefinite skin allograft survival across fully mismatched mouse strain combinations. We investigated the role of chimerism in this transplantation tolerance model. B10.A (H-2a) mice were treated with ALS on day -1 and 2, sirolimus, and infusion of (C57BL/6xDBA/2)F1 (B6D2F1, H-2(b/d)) BMCs on day 7 relative to DBA/2 (D2) skin grafting on day 0. At postgraft days 30, 50 and 120, the recipient mice were injected intravenously with splenocytes prepared from either naive or D2 mixed chimeric B10.A mice that had been sensitized in vivo to B6. Changes in chimerism and graft survival were monitored. Although D2 skin grafts were rejected with a median survival time of 63.8 days in B10.A mice given ALS and sirolimus alone, they survived more than 200 days in all B10.A mice given ALS, sirolimus, and B6D2F1 BMCs. Chimerism became evident 21 days postgrafting and progressively increased thereafter to 20% at postgraft day 200. Infusion of anti-B6 presensitized cells resulted in depletion of chimeric donor cells and subsequent graft rejection regardless of the timing of injection. Injection of presensitized cells in mice given ALS...Continue Reading

References

Jun 27, 1992·Lancet·T E StarzlM Trucco
Jun 1, 1993·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·T E StarzlJ J Fung
Dec 1, 1996·Immunology Today·K Wood, D H Sachs
Jan 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Akira Kanamoto, Takashi Maki

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Citations

Apr 17, 2012·The Journal of Surgical Research·Naoko KutsunaTadatoshi Takayama
May 10, 2013·Clinical and Experimental Immunology·S YamazakiT Takayama
Aug 9, 2005·Current Opinion in Immunology·Tatsuo IchinoheHiroh Saji

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