SUPPRESSION OF DELAYED XENOGRAFT REJECTION BY SPECIFIC DEPLETION OF ELICITED ANTIBODIES OF THE IgM ISOTYPE1
- 1 September 1999
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Transplantation
- Vol. 68 (6), 844-854
- https://doi.org/10.1097/00007890-199909270-00018
Abstract
Background, Hamster hearts transplanted into untreated rats undergo delayed xenograft rejection (DXR). This acute inflammatory response is associated with the deposition of anti-graft antibodies of the immunoglobulin (Ig)M isotype in the vasculature. We have previously shown that these antibodies are generated in a T cell-independent manner. In this study, we tested whether the generation of anti-graft IgM antibodies is involved in the pathogenesis of DXR. in addition, we tested whether the suppression of this antibody response mould overcome DXR. Methods. Hamster hearts were transplanted into rats treated with an anti-mu monoclonal antibodies (mAb) to deplete circulating IgM or with an isotype-matched control mAb recognizing the dinitrophenyl epitope. T cell immunosuppression was achieved with cyclosporin A (CsA). Results. Depletion of circulating IgM by anti-mu mAb inhibited DXR, whereas the control mAb had no effect on DXR. In anti-mu-treated rats, xenografts were rejected 5-7 days after transplantation through a T cell-dependent mechanism associated with the generation of antibodies of the IgG isotype. Combination of anti-mu with CsA suppressed the anti-graft IgM and IgG response and resulted in long-term xenograft survival (> 50 days). Xenograft long term survival occurred despite the return of anti-graft IgM antibodies to the circulation, a phenomenon referred to as accommodation. Conclusion. This study demonstrates that the pathogenesis of DXR can be initiated by anti-graft antibodies of the IgM isotype, which are generated in a T-cell independent manner. In addition, we show that under T cell immunosuppression, specific depletion of this IgM response by anti-mu mAb administration results in xenograft long-term survival and accommodationKeywords
This publication has 19 references indexed in Scilit:
- TRANSIENT COMPLEMENT INHIBITION PLUS T-CELL IMMUNOSUPPRESSION INDUCES LONG-TERM SURVIVAL OF MOUSE-TO-RAT CARDIAC XENOGRAFTS1, 2Transplantation, 1998
- EFFECT OF CONTINUOUS COMPLEMENT INHIBITION USING SOLUBLE COMPLEMENT RECEPTOR TYPE 1 ON SURVIVAL OF PIG-TO-PRIMATE CARDIAC XENOGRAFTS1Transplantation, 1997
- P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflamed tissuesNature, 1997
- T CELL INDEPENDENCE OF MACROPHAGE AND NATURAL KILLER CELL INFILTRATION, CYTOKINE PRODUCTION, AND ENDOTHELIAL ACTIVATION DURING DELAYED XENOGRAFT REJECTION1,2,3Transplantation, 1996
- Delayed xenograft rejectionImmunology Today, 1996
- Activated platelets signal chemokine synthesis by human monocytes.JCI Insight, 1996
- Guidelines for XenotransplantationScience, 1995
- ACTIVATION OF INTRAGRAFT ENDOTHELIAL AND MONONUCLEAR CELLS DURING DISCORDANT XENOGRAFT REJECTIONTransplantation, 1994
- THE SYNERGISTIC EFFECT OF COMBINED ANTIBODY AND COMPLEMENT DEPLETION ON DISCORDANT CARDIAC XENOGRAFT SURVIVAL IN NONHUMAN PRIMATES1,2Transplantation, 1994
- EVIDENCE THAT LONG-TERM SURVIVAL OF CONCORDANT XENOGRAFTS IS ACHIEVED BY INHIBITION OF ANTISPECIES ANTIBODY PRODUCTIONTransplantation, 1992