The effects of nondepleting CD4 targeted therapy in presensitized rat recipients of cardiac allografts

Transplantation
J BinderJ W Kupiec-Weglinski

Abstract

The immunosuppressive effects of RIB-5/2, a nondepleting anti-rat CD4 monoclonal antibody (mAb), were analyzed in a well-defined model of accelerated cardiac allograft rejection. (LEW x BN)F1 hearts are rejected within 24 hours in LEW hosts presensitized with BN skin grafts at day -7. Treatment with RIB-5/2 mAb (3.5 mg/day i.v.) at days -7 and -1, prolonged cardiac allograft survival to the median of >62 days. The long-term recipients rejected acutely third-party (Wistar-Furth) test skin grafts, without an adverse effect on the survival of the original cardiac transplants. Lymphocytes harvested from mAb-treated hosts significantly decreased proliferative responses of donor cells in mixed leukocyte reaction. The cell activation and cytokine elaboration patterns were evaluated at the mRNA and protein levels by competitive template reverse transcriptase polymerase chain reaction and immunohistochemistry, respectively. Cardiac allografts in CD4 mAb-treated rats at 24 hours displayed reduced CD3, CD25, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-2, interferon (IFN)-gamma, and IL-10 mRNA levels as compared to those in rejecting grafts. Equal amounts of IL-4 mRNA were detected throughout in both animal groups; the expressi...Continue Reading

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Citations

May 1, 1997·Transplantation Proceedings·K OnoderaJ W Kupiec-Weglinski
Oct 1, 1996·Current Opinion in Immunology·T B StromA Bushell
Oct 6, 1999·Current Opinion in Immunology·Y Zhai, J W Kupiec-Weglinski
Nov 17, 2010·Transplantation·Zhu LanHao Wang
Nov 26, 2010·Immunotherapy·Marshall Strome, David G Lott
May 19, 2010·Expert Review of Clinical Immunology·Thomas Ritter, Uwe Pleyer
May 1, 2008·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·R P RotherH Wang
Jul 17, 2013·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·A SiepertB Sawitzki
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Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hao WangRobert Zhong
Sep 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dawn Winsor-HinesPaul D Ponath

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