Prolonged survival of rat islet xenografts in mice after CD45RB monotherapy

Visser, Lydia; Poppema, Sibrand; Haan, Bart de; Klok, Pieter; Leij, Judith van der; Berg, Anke van den; Vos, Paul de

doi:10.1097/01.tp.0000111741.85249.ec

Cited by 12 publications

(8 citation statements)

References 30 publications

(31 reference statements)

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“…We have previously shown that treatment of chemically diabetic C57BL/6 mice with DST and anti-CD154 mAb leads to prolonged survival of rat islet and skin xenografts (17,18) and xenogeneic neonatal porcine islet cell clusters (19). Similarly, anti-CD45RB mAb (20), anti-CD4 mAb (21), or coadministration of CTLA4-Fc and anti-CD154 mAb (22,23) leads to prolonged islet xenograft survival in mice. Islet xenograft tolerance has also been reported in monkeys given anti-CD3 immunotoxin, cyclosporine, and steroids (24).…”

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confidence: 99%

Autoimmune Diabetes and Resistance to Xenograft Transplantation Tolerance in NOD Mice

et al. 2005

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Costimulation blockade induces prolonged rat islet and skin xenograft survival in C57BL/6 mice. Nonobese diabetic (NOD) mice, which are used to model human autoimmune diabetes, are resistant to costimulation blockade-induced allograft tolerance. We tested the hypothesis that NOD mice would also be resistant to costimulation blockade-induced rat xenograft tolerance. We report that rat islet xenograft survival is short in spontaneously diabetic NOD mice treated with a tolerizing regimen of donor-specific transfusion and anti-CD154 antibody. Rat islet xenograft survival is only marginally longer in chemically diabetic NOD mice treated with costimulation blockade but is prolonged further in NOD Idd congenic mice bearing C57-derived chromosome 3 loci. Reciprocally, the presence of NODderived chromosome 3 loci shortens islet xenograft survival in tolerized C57BL/6 mice. Islet xenograft survival is longer in tolerized NOD.CD4aϪ/Ϫ and (NOD ؋ C57BL/6)F1 mice than in NOD mice but still much shorter than in C57BL/6 mice. Skin xenograft survival in (NOD ؋ C57BL/6)F1 mice treated with costimulation blockade is short, suggesting a strong genetic resistance to skin xenograft tolerance induction. We conclude that the resistance of NOD mice to xenograft tolerance induction involves some mechanisms that also participate in the expression of autoimmunity and other mechanisms that are distinct. Diabetes 54:107-115, 2005

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confidence: 99%

Autoimmune Diabetes and Resistance to Xenograft Transplantation Tolerance in NOD Mice

et al. 2005

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“…According to previous reports, the expression levels of cytokine mRNAs in type 1 T helper cells (Th1s) and type 2 T helper cells (Th2s) in xenograft-bearing kidneys was decreased after anti-CD45RB treatment of chemically induced diabetic B6 mice (16). Another recent study in rodents indicates that Th1 and Th2 cytokines must both be thwarted in order to induce robust tolerance and prevent chronic rejection (31).…”

Section: Discussionmentioning

confidence: 92%

“…CD45RB is a restricted isoform of CD45 that has been an effective target of mAb therapy for the induction of tolerance and prolongation of allograft and xenograft survival in experimental models of islet transplantation (14,15). Treatment of islet transplantation recipients with either anti-CD45RB (a signal 1 inhibitor) alone or anti-CD45RB plus anti-CD154 (a signal 2 inhibitor) promotes long-term islet allograft survival in mice with chemically induced diabetes (16) and in spontaneously diabetic nonobese diabetic (NOD) mice (17). Taken together, these results reveal that TCR signaling (signal 1) and co-stimulation (signal 2) constitute promising targets for pharmaceuticals that prolong islet graft survival.…”

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confidence: 99%

Beneficial Effects of Simultaneous Treatment With 15-deoxyspergualin and Monoclonal Antibodies to CD45RB and CD154 on Murine Islet Transplantation Recipients

Jung

Lee

et al. 2006

Transplantation

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“…CD45RB antibody, a newly developed tolerance-inducing drug, not only induces immune tolerance but maintains immunosuppressive status, leading to prolonged survival time of grafts [31]. Administration of CD45RB antibody in allogeneic or xenogenic pancreatic islet transplantation can induce immune tolerance and prolong the survival time of transplanted pancreatic islets [32]. In the animals receiving pancreatic islet transplantation and CD45RB antibody, the Th1 to Th2 shift and Tc1 to Tc2 shift.…”

Section: Discussionmentioning

confidence: 99%

Immune modulation of co-transplantation mesenchymal stem cells with islet on T and dendritic cells

Wang

Deng

et al. 2010

Clinical and Experimental Immunology

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SummaryAllogeneic pancreatic islet transplantation theoretically represents a cure for type 1 diabetes. However, current immune suppressive therapies are often associated with undesired side effects. Given this problem, and the shortage of human islet donors, the majority of type 1 diabetes patients cannot currently be offered an islet transplant. However, it has been found that mesenchymal stem cells (MSCs) could exert unique immunosuppressive effects both in vitro and in vivo. Herein we transplanted allogeneic 200 islets alone or in combination with MSCs (3 ¥ 10 6 cells) under the kidney capsules of diabetic C57LB/6 mouse. We found that the ratios of T helper type 1 (Th1) to Th2 and Tc1 to Tc2 were reduced, and the numbers of naive and memory T cells were down-regulated in peripheral blood after transplantation. In addition, the maturation, endocytosis and interleukin-12 secretion of dendritic cell (DCs)-derived bone marrow cells (BMCs) from receptor mice were suppressed. Rejection reaction was alleviated by MSCs which exerted suppressive effects through T lymphocyte subsets and DCs.

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Prolonged survival of rat islet xenografts in mice after CD45RB monotherapy

Abstract: Our results show that a short course of anti-CD45RB monotherapy prolongs the survival of rat islet xenografts in C57BL/6 mice.

Cited by 12 publications

References 30 publications

Autoimmune Diabetes and Resistance to Xenograft Transplantation Tolerance in NOD Mice

Autoimmune Diabetes and Resistance to Xenograft Transplantation Tolerance in NOD Mice

Beneficial Effects of Simultaneous Treatment With 15-deoxyspergualin and Monoclonal Antibodies to CD45RB and CD154 on Murine Islet Transplantation Recipients

Immune modulation of co-transplantation mesenchymal stem cells with islet on T and dendritic cells

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