Superagonistic CD28 antibody induces donor-specific tolerance in rat renal allografts

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
H AzumaShiro Takahara

Abstract

The ultimate goal of organ transplantation is to establish graft tolerance where CD4+CD25+FOXP3+ regulatory T (Treg) cells play an important role. We examined whether a superagonistic monoclonal antibody specific for CD28 (CD28 SA), which expands Treg cells in vivo, would prevent acute rejection and induce tolerance using our established rat acute renal allograft model (Wistar to Lewis). In the untreated or mouse IgG-treated recipients, graft function significantly deteriorated with marked destruction of renal tissue, and all rats died by 13 days with severe azotemia. In contrast, 90% of recipients treated with CD28 SA survived over 100 days, and 70% survived with well-preserved graft function until graft recovery at 180 days. Analysis by flow cytometry and immunohistochemistry demonstrated that CD28 SA induced marked infiltration of FOXP3+ Treg cells into the allografts. Furthermore, these long-surviving recipients showed donor-specific tolerance, accepting secondary (donor-matched) Wistar cardiac allografts, but acutely rejecting third-party BN allografts. We further demonstrated that adoptive transfer of CD4+CD25+ Treg cells, purified from CD28 SA-treated Lewis rats, significantly prolonged allograft survival and succeeded i...Continue Reading

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Citations

Apr 15, 2010·Medical Microbiology and Immunology·Thomas HünigFrank Brombacher
Nov 16, 2010·Clinical and Experimental Nephrology·Kenro MiyasatoYoshitaka Isaka
Oct 3, 2013·Expert Opinion on Biological Therapy·Leonardo V Riella, Mohamed H Sayegh
Mar 10, 2009·Medicinal Research Reviews·Zhu ShenJinjin Wu
May 12, 2009·Immunological Reviews·Xian C LiMohamed H Sayegh
Apr 5, 2012·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·N PoirierB Vanhove
Oct 23, 2010·Transplant International : Official Journal of the European Society for Organ Transplantation·Nicolas PoirierBernard Vanhove
Jan 15, 2014·Transplant International : Official Journal of the European Society for Organ Transplantation·Koji SugimotoShinichi Matsumoto
Oct 17, 2013·International Reviews of Immunology·Pasquale EspositoAntonio Dal Canton
May 20, 2015·Transplantation Direct·Steven L RosinskiScott S Graves
Oct 25, 2016·Transplantation·Paolo MalvezziLionel Rostaing
Feb 15, 2018·Frontiers in Immunology·Daniela LangenhorstThomas Hünig
Feb 15, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Toyofumi AbeNorio Nonomura

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