Postnatal xenogeneic B-cell tolerance in swine followingin uterointraportal antigen exposure
| Autor: | Nalu Navarro Alvarez, Parsia A. Vagefi, Alexander Y. Zhu, David H. Sachs, J S Arn, Michael Duggan, Ronald S. Arellano, Mark A. Randolph, Christene A. Huang |
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| Rok vydání: | 2015 |
| Předmět: |
Swine
Transplantation Heterologous Immunology Antibodies Heterophile Biology Immune tolerance Immune system Antigen Pregnancy Antigens Heterophile biology.animal Immune Tolerance medicine Animals B cell Bone Marrow Transplantation B-Lymphocytes Transplantation Fetus Immunity Humoral medicine.anatomical_structure In utero Prenatal Exposure Delayed Effects Female Bone marrow Papio Baboon |
| Zdroj: | Xenotransplantation. 22:368-378 |
| ISSN: | 0908-665X |
| Popis: | Background The objective of this study was to investigate the humoral immune response to xenogeneic antigens administered during the fetal state utilizing a baboon-to-pig model. Methods Nine fetuses from an alpha-1,3-galactosyltransferase gene knockout (GalT-KO) MGH-miniature swine sow underwent transuterine ultrasound-guided intraportal injection of T-cell depleted baboon bone marrow (B-BM) at mid-gestation. Two juvenile GalT-KO swine undergoing direct B-BM intraportal injection were used as controls. Results Postnatal humoral tolerance was induced in the long-term surviving piglets as demonstrated by the absence of any antibody response to baboon donor cells. In addition, a second intraportal B-BM administration at 2.5 months post-birth led to no antibody formation despite re-exposure to xenogeneic antigens. This B-cell unresponsiveness was abrogated only when the animal was exposed subcutaneously to third-party xenogeneic and allogeneic antigens, suggesting that the previously achieved humoral non-responsiveness was donor specific. In comparison, the two juvenile GalT-KO control swine demonstrated increasing anti-baboon IgM and IgG levels following intraportal injection. Conclusions In summary, xenogeneic B-cell tolerance was induced through in utero intraportal exposure to donor cells and this tolerance persisted following postnatal rechallenge with donor B-BM, but was lost on exposure to third-party antigen, possibly as a result of cross-reactive antibody formation. |
| Databáze: | OpenAIRE |
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