Experimental Renal Heterotransplantation

Perper, R. J.; Najarían, John S.

doi:10.1097/00007890-196607000-00002

Cited by 154 publications

(51 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2) and deposition of those antibodies in the graft (Fig. 3 A , top ), a result consistent with previous studies (3,19,40). Anti-Gal ␣ 1-3Gal IgM in particular was undetectable in the blood of recipients after transplantation, confirming the idea that anti-Gal ␣ 1-3Gal IgM is a major specificity of antibodies adsorbed by pig-to-primate xenografts, and is involved in the pathogenesis of hyperacute xenograft rejection (41).…”

Section: Development Of Acute Vascular Rejection In Baboonssupporting

confidence: 90%

The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants.

Lin

Weidner²,

Byrne³

et al. 1998

J. Clin. Invest.

259

161

View full text Add to dashboard Cite

Long-term success in xenotransplantation is currently hampered by acute vascular rejection. The inciting cause of acute vascular rejection is not yet known; however, a variety of observations suggest that the humoral immune response of the recipient against the donor may be involved in the pathogenesis of this process. Using a pig-to-baboon heterotopic cardiac transplant model, we examined the role of antibodies in the development of acute vascular rejection. After transplantation into baboons, hearts from transgenic pigs expressing human decay-accelerating factor and CD59 underwent acute vascular rejection leading to graft failure within 5 d; the histology was characterized by endothelial injury and fibrin thrombi. Hearts from the transgenic pigs transplanted into baboons whose circulating antibodies were depleted using antiimmunoglobulin columns (Therasorb, Unterschleisshein, Germany) did not undergo acute vascular rejection in five of six cases. Biopsies from the xenotransplants in Ig-depleted baboons revealed little or no IgM or IgG, and no histologic evidence of acute vascular rejection in the five cases. Complement activity in the baboons was within the normal range during the period of xenograft survival. In one case, acute vascular rejection of a xenotransplant occurred in a baboon in which the level of antidonor antibody rose after Ig depletion was discontinued. This study provides evidence that antibodies play a significant role in the pathogenesis of acute vascular rejection, and suggests that acute vascular rejection might be prevented or treated by therapies aimed at the humoral immune response to porcine antigens. (

show abstract

Section: Development Of Acute Vascular Rejection In Baboonssupporting

confidence: 90%

The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants.

Lin

Weidner²,

Byrne³

et al. 1998

J. Clin. Invest.

259

161

View full text Add to dashboard Cite

show abstract

“…4B). The hearts had histopathologic findings of rejection similar to those reported previously (14), DISCUSSION The therapeutic implication of inhibiting or depleting complement has been a recurring theme of transplantation research since the HAR syndromes were recognized in allograft recipients who had preformed antigraft antibodies (15)(16)(17), the same events were described in discordant xenotransplant models (18), and Gewurz et a1. (19) demonstrated that the HAR of organ allografts and xenografts was a complement activation syndrome.…”

Section: ~------------------------supporting

confidence: 67%

Effect of Anticomplement Agent K76 Cooh on Hamster-to-Rat and Guinea Pig-to-Rat Heart Xenotransplantation1

Tanaka

Murase²,

Ye³

et al. 1996

Transplantation

View full text Add to dashboard Cite

“…Xenoreactive immunity is very vigorous; hence, a profound form of immunosuppression and/or immunomanipulation will be needed to prevent rejection of xenografts. The first form of xenorejection, hyperacute rejection, occurs upon reperfusion of xenografts by the recipient blood because of binding of natural xenoantibodies to endothelial cells of the graft and activation of the complement system (1,2). This can be overcome by interfering with the complement system, e.g., by using genetically modified donors (3).…”

Section: Pathogenesis Of Autoimmunity After Xenogeneic Thymus Transplmentioning

confidence: 99%

Pathogenesis of Autoimmunity After Xenogeneic Thymus Transplantation

Yan

Devos

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

Thymus transplantation is a promising strategy to induce xenotolerance, but may also induce an autoimmune syndrome (AIS). The pathogenesis of this AIS was explored using nude rats as recipients. Thymus grafts consisted of fetal hamster thymic tissue with or without mixing with fetal rat tissue such as thymus, thyroid, salivary gland, and heart. All hamster thymus recipients died of AIS within 2–3 mo. In most recipients of xenothymus mixed with rat tissues such as thymus, thyroid, and salivary gland, but not heart, AIS was prevented, indicating an insufficient presence of rat epithelial cell Ags within the xenothymus. AIS could be transferred to control nude rats by whole splenocytes or by splenocyte subpopulations such as CD3+, CD3−, and B lymphocytes, but not by non-T, non-B cells from AIS animals. This transfer could be suppressed by cotransferring either CD4+ or CD8+ lymphocytes from euthymic rats, but not by splenocytes from recipients of syngeneic or xenogeneic thymus mixed with rat tissue, indicating a defective generation of regulatory lymphocytes. As for CD4+ regulatory cells this defect was probably qualitative, because the percentages of CD4+CD25+ or CD4+CD45RClow populations were normal after xenothymus transplantation. As for the CD8+ regulatory cells, the defect was quantitative, as CD8+ cell levels always remained low. The latter was related to the nonvascularized nature of thymus grafts. In conclusion, AIS after xenothymus transplantation in nude rats is due to a combination of insufficient intrathymic presence of host-type epithelial cell Ags and a defective generation of regulatory T lymphocytes.

show abstract

Experimental Renal Heterotransplantation

Cited by 154 publications

References 0 publications

The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants.

The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants.

Effect of Anticomplement Agent K76 Cooh on Hamster-to-Rat and Guinea Pig-to-Rat Heart Xenotransplantation1

Pathogenesis of Autoimmunity After Xenogeneic Thymus Transplantation

Contact Info

Product

Resources

About