Prolongation of Renal Allograft Survival in Antilymphocyte-Serum-Treated Dogs by Postoperative Injection of Density-Gradient-Fractionated Donor Bone Marrow

Hartner, William C.; Fazio, S. R. De; Maki, Takashi; Markees, Thomas G.; Monaco, Anthony P.; Gozzo, J J

doi:10.1097/00007890-198612000-00004

Cited by 48 publications

(16 citation statements)

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“…Long-term survival in about a third of the dogs in group 2 is comparable with results achieved in primates using total lymphoid irradiation [ 16] or with rabbit antithymocyte globulin and donor bone marrow [17], How ever, this degree of success has not been achieved in the mongrel renal allograft model using rabbit antilymphocyte globulin and donor bone marrow [18], nor with chemical immunosuppression, although spo radic cases of long-term survival after cessa tion of therapy have been reported [19,20], In outbred large animals it is possible that the long-term survivors following allograft ing with immunosuppression are genetically determined low responders to donor trans plantation antigens or are partially histocompatible. In dogs, we and others [8,21] find that kidney grafts in untreated mongrels are always rejected in less than 14 days.…”

Section: Discussionsupporting

confidence: 53%

Long-Term Survival of Kidney Allografts in Dogs after Withdrawal of Immunosuppression with Ciclosporin and Azathioprine

Davies

Collier²,

Thiru³

et al. 1989

Eur Surg Res

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We have examined the immunosuppressive effects of combined azathioprine (Aza) and ciclosporin (CS) in two groups of mongrel dogs receiving kidney allografts. In group 1 Aza and CS were given together daily after transplantation and in group 2 twice the dose of each drug was given separately on alternate days. Doses were halved in each group at successive 84-day intervals and all immunosuppression was stopped on day 336. Thus the same total amounts of Aza and CS were given to all recipients in both groups. Up to day-60 the incidence of rejection in each group was similar, thereafter recipients in group 1 were more susceptible to fatal infection and marrow hypoplasia. This accounted for the difference in long-term survival between the two groups (1/14 in group 1, 5/12 in group 2 at day 420). Subsequently, two long-term survivors in group 2 died, 1 on day 452 from chronic rejection and the other on day 529 from gastroenteritis with a histologically normal allograft kidney. An in vitro analysis of the alloreactive repertoire of two healthy recipients in group 2, bearing each other’s kidneys for more than 2.5 years and more than 500 days without immunosuppression, showed a profound donor-specific defect which could account for their operationally tolerant state.

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Section: Discussionsupporting

confidence: 53%

Long-Term Survival of Kidney Allografts in Dogs after Withdrawal of Immunosuppression with Ciclosporin and Azathioprine

Davies

Collier²,

Thiru³

et al. 1989

Eur Surg Res

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“…This hypothesis was based on a number of animal studies [4][5][6][7] and on the observations of Starzl et al 13,36 previously mentioned.…”

Section: Regulatory Functions Of Rdd Chimeric Cellsmentioning

confidence: 99%

“…2,3 Subsequently, it was demonstrated that post-or peri-transplant infusion of donor bone marrow cells together with T cell depletion prolonged and sometimes brought about indefinite allograft survival in adult murine, canine and primate recipients in the absence of chronic immunosuppression. [4][5][6][7] These observations have for the most part been associated with the development of chimerism, but a cause and effect relationship has been the subject of controversy. 8 The first clinical attempt to use donor bone marrow cells in human solid organ transplantation was that of Monaco et al 9 in kidney transplants performed in Boston with concomitant polyclonal anti-lymphocyte globulin induction therapy.…”

Section: Introduction and Brief Historymentioning

confidence: 99%

Immunoregulatory role of chimerism in clinical organ transplantation

Mathew

Miller

2001

Bone Marrow Transplant

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“…Tolerant mice showed evidence of low degree (up to 4%) chimerism (microchimerism) (3). Subsequent studies in mongrel dogs (4,5) and nonhuman primates (6,7) demonstrated that the use of polyclonal ALS and donor BMC is also very effective in producing tolerance to kidney allografts. Posttransplant donor BMC infusion with induction therapy by polyclonal antilymphocyte globulin was clinically applied in living-related and cadaveric kidney transplantation with a standard multidrug immunosuppressive protocol (8 -10).…”

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confidence: 99%

Donor MHC Class II Antigen Is Essential for Induction of Transplantation Tolerance by Bone Marrow Cells

Umemura

Monaco

Maki

2000

The Journal of Immunology

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Posttransplant infusion of donor bone marrow cells (BMC) induces tolerance to allografts in adult mice, dogs, nonhuman primates, and probably humans. Here we used a mouse skin allograft model and an allogeneic radiation chimera model to examine the role of MHC Ags in tolerance induction. Infusion of MHC class II Ag-deficient (CIID) BMC failed to prolong C57BL/6 (B6) skin grafts in ALS- and rapamycin-treated B10.A mice, whereas wild-type B6 or MHC class I Ag-deficient BMC induced prolongation. Removal of class II Ag-bearing cells from donor BMC markedly reduced the tolerogenic effect compared with untreated BMC, although graft survival was significantly longer in mice given depleted BMC than that in control mice given no BMC. Infusion of CIID BMC into irradiated syngeneic B6 or allogeneic B10.A mice produced normal lymphoid cell reconstitution including CD4+ T cells except for the absence of class II Ag-positive cells. However, irradiated B10.A mice reconstituted with CIID BMC rejected all B6 and a majority of CIID skin grafts despite continued maintenance of high degree chimerism. B10.A mice reconstituted with B6 BMC maintained chimerism and accepted both B6 and CIID skin grafts. Thus, expression of MHC class II Ag on BMC is essential for allograft tolerance induction and peripheral chimerism with cells deficient in class II Ag does not guarantee allograft acceptance.

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Prolongation of Renal Allograft Survival in Antilymphocyte-Serum-Treated Dogs by Postoperative Injection of Density-Gradient-Fractionated Donor Bone Marrow

Cited by 48 publications

References 0 publications

Long-Term Survival of Kidney Allografts in Dogs after Withdrawal of Immunosuppression with Ciclosporin and Azathioprine

Long-Term Survival of Kidney Allografts in Dogs after Withdrawal of Immunosuppression with Ciclosporin and Azathioprine

Immunoregulatory role of chimerism in clinical organ transplantation

Donor MHC Class II Antigen Is Essential for Induction of Transplantation Tolerance by Bone Marrow Cells

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