2000
DOI: 10.1097/00007890-200012270-00002
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The Role of Anti-Gal??1-3gal Antibodies in Acute Vascular Rejection and Accommodation of Xenografts1

Abstract: These results demonstrate that anti-Galalpha1-3Gal antibodies cause acute vascular rejection and suggest that depletion of these antibodies leads to accommodation of the donor cardiac xenograft and could supply an important model for additional study.

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Cited by 140 publications
(109 citation statements)
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“…This can be achieved by affinity column expressing synthetic a-gal epitopes. [29][30][31] Since the transduction of lymphocytes by AdaGT will be performed in vitro, it is probable that this method of gene therapy will not be affected by factors limiting in vivo gene therapy by adenovirus vectors, such as immune response to the virus. 40 The relevance of this method for induction of tolerance to a-gal epitopes in humans will first have to be tested in monkeys in order to determine whether this phenomenon, which is observed in mice, is also applicable to primates.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…This can be achieved by affinity column expressing synthetic a-gal epitopes. [29][30][31] Since the transduction of lymphocytes by AdaGT will be performed in vitro, it is probable that this method of gene therapy will not be affected by factors limiting in vivo gene therapy by adenovirus vectors, such as immune response to the virus. 40 The relevance of this method for induction of tolerance to a-gal epitopes in humans will first have to be tested in monkeys in order to determine whether this phenomenon, which is observed in mice, is also applicable to primates.…”
Section: Discussionmentioning
confidence: 99%
“…22 This elicited anti-Gal can destroy cells expressing a-gal epitopes; therefore, PKM-immunized KO mice are not suitable for studying tolerance induction by AdaGT transduced lymphocytes. Whereas anti-Gal can be effectively removed in primates by affinity columns expressing a-gal epitopes, [29][30][31] such a treatment is technically not feasible in mice. Nevertheless, the detrimental effect of anti-Gal could be avoided in this experimental model by adoptive transfer of 20 Â 10 6 lymphocytes from PKM-immunized KO mice (ie lymphocytes including memory anti-Gal B cells) and 20 Â 10 6 naïve KO bone marrow cells into lethally irradiated KO recipients.…”
Section: Tolerization Of Memory Anti-gal B Cellsmentioning
confidence: 99%
“…HAR and AVR, following pig to primate organ xenotransplantation are to a large extent also Ab mediated [5]. Even though the exact mechanisms causing acute vascular xenograft rejection are not known, graftinduced Ab [30], which may be of the § -Gal specificity [31], are thought to be important for its pathogenesis. We hypothesized that anti- § -Gal Ab in the absence of complement would influence NK cell adhesion to, and migration across, porcine endothelium by either, or a combination, of two mechanisms: (i) by Ab-mediated endothelial cell activation or (ii) by Fc receptor cross-linking triggering NK cell motility.…”
Section: Discussionmentioning
confidence: 99%
“…Generally, the model systems used involve the transplantation of organs between disparate species, and the recipients of these transplants had natural and acquired antibodies specific for the grafts [11,21,22]. In these model systems we found that depletion of all immunoglobulin or species-specific immunoglobulin could allow survival of the organ graft and accommodation to ensue (Figure 1) [23,24]. Figure 1 shows the levels of xenoreactive antibodies in the blood of a xenograft recipient from which antibody was depleted from the time of transplantation.…”
Section: Accommodation In Experimental Modelsmentioning
confidence: 95%