Transgenic anti-CD4 monoclonal antibody secretion by mouse segmental pancreas allografts promotes long term survival
- Author(s)
- Mottram, PL; Murray-Segal, LJ; Han, WR; Zhan, YF; Brady, JL; Lew, AM;
- Details
- Publication Year 2000-11,Volume 8,Issue #3,Page 203-209
- Journal Title
- TRANSPLANT IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- To compare the effectiveness of transgenic and systemic monoclonal antibody therapy for pancreas transplantation, vascularised segmental pancreas allografts from wild-type or transgenic pancreatic tissue that secreted monoclonal anti-CD4 were placed in CBA recipients in which diabetes had been induced chemically by streptozotocin (STZ, non-autoimmune diabetes). In untreated CBA recipients, wild-type BALB/c or C57BL/6 bm1 pancreas transplants were rejected in a mean survival time (MST) of 27 and 30 days, respectively. BALB/c and C57BL/6 graft survival improved when recipients were given a short course of T cell depleting monoclonal anti-CD4 antibody, (GK 1.5, 2 mg total on days -1, 0, 1, 2 with grafting on day 0) with MST +/- S.D. of 71 +/- 29 and 44 +/- 36 days, respectively. Thus, transient depletion of CD4 was effective in delaying pancreas allograft rejection in these strain combinations. The use of C57BL/6 bm1 mice transgenic for a rat anti-CD4 antibody (GK5 mice) as pancreas donors provided allografts that secreted sufficient anti-CD4 antibody to cause CD4 T cell depletion in the recipients (CD4 cells decreased from 30 to < 5% of small lymphocytes). This degree of depletion was not sustained and the CD4 recovery inversely correlated with graft survival. Mice with > 20% CD4 cells in the splenic lymphocyte population 4 weeks post-transplant rejected their grafts (3 of 10 mice). However, in 7 of 10 mice CD4 cells remained low(< 15%) and allografts survived for > 80 days. The GK5 allografts survived significantly longer than those from non-transgenic bm1 controls (MST 83 +/- 32 days, compared with 30 days, P < 0.0005). This survival time was similar to that of BALB/c allografts in CBA recipients treated with a high dose of anti-CD4 antibody. Thus, transgenic secretion of anti-CD4 antibody by the pancreas allograft was very effective in prolonging its survival. (C) 2000 Elsevier Science B.V. All rights reserved.
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- LOCAL IMMUNOSUPPRESSIVE THERAPY; CYTOKINE MESSENGER-RNA; PERIPHERAL TOLERANCE; GRAFT-REJECTION; TRANSPLANTATION; ISLET; MICE; CYCLOSPORINE; MECHANISMS; EXPRESSION
- Publisher's Version
- https://doi.org/10.1016/S0966-3274(00)00028-9
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2000-11-01 12:00:00