Prenatal Tolerance Induction: Relationship between Cell Dose, Marrow T-Cells, Chimerism, and Tolerance
It was reported that the dose of self-antigens can determine the consequence of deletional tolerance and donor T cells are critical for tolerance induction in mixed chimeras. This study aimed at assessing the effect of cell doses and marrow T cells on engraftment and tolerance induction after prenat...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2008-05-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368908785095971 |
| _version_ | 1818940476240166912 |
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| author | Jeng-Chang Chen M.D. Ming-Ling Chang Shiu-Feng Huang Pei-Yeh Chang Marcus O. Muench Ren-Huei Fu Liang-Shiou Ou Ming-Ling Kuo |
| author_facet | Jeng-Chang Chen M.D. Ming-Ling Chang Shiu-Feng Huang Pei-Yeh Chang Marcus O. Muench Ren-Huei Fu Liang-Shiou Ou Ming-Ling Kuo |
| author_sort | Jeng-Chang Chen M.D. |
| collection | DOAJ |
| description | It was reported that the dose of self-antigens can determine the consequence of deletional tolerance and donor T cells are critical for tolerance induction in mixed chimeras. This study aimed at assessing the effect of cell doses and marrow T cells on engraftment and tolerance induction after prenatal bone marrow transplantation. Intraperitoneal cell transplantation was performed in FVB/N (H-2Kq) mice at gestational day 14 with escalating doses of adult C57BL/6 (H-2Kb) marrows. Peripheral chimerism was examined postnatally by flow cytometry and tolerance was tested by skin transplantation. Transplantation of light-density marrow cells showed a dose response. High-level chimerism emerged with a threshold dose of 5.0 × 106 and host leukocytes could be nearly replaced at a dose of 7.5–10.0 × 106. High-dose transplants conferred a steady long-lasting donor-specific tolerance but were accompanied by >50% incidence of graft-versus-host disease. Depletion of marrow T cells lessened graft-versus-host disease to the detriment of engraftment. With low-level chimerism, tolerance was a graded phenomenon dependent upon the level of chimerism. Durable chimerism within 6 months required a threshold of = 2% chimerism at 1 month of age and predicted a 50% chance of long-term tolerance, whereas transient chimerism (<2%) only caused hyporesponsiveness to the donor. Tolerance induction did not succeed without peripheral chimerism even if a large amount of injected donor cells persisted in the peritoneum. Neither did an increase in cell doses or donor T-cell contents benefit skin graft survivals unless it had substantially improved peripheral chimerism. Thus, peripheral chimerism level can be a simple and straightforward test to predict the degree of prenatal immune tolerance. |
| first_indexed | 2024-12-20T06:40:15Z |
| format | Article |
| id | doaj.art-e5a2a7821adf43e28d1df3e2f7b9a9a2 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-20T06:40:15Z |
| publishDate | 2008-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-e5a2a7821adf43e28d1df3e2f7b9a9a22022-12-21T19:49:52ZengSAGE PublishingCell Transplantation0963-68971555-38922008-05-011710.3727/096368908785095971Prenatal Tolerance Induction: Relationship between Cell Dose, Marrow T-Cells, Chimerism, and ToleranceJeng-Chang Chen M.D.0Ming-Ling Chang1Shiu-Feng Huang2Pei-Yeh Chang3Marcus O. Muench4Ren-Huei Fu5Liang-Shiou Ou6Ming-Ling Kuo7Department of Surgery, Chang Gung Children's Hospital, Chang Gung University College of Medicine, Taoyuan, TaiwanDepartment of Hepatogastroenterology, Chang Gung Memorial Hospital, Taoyuan, TaiwanDivision of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, TaiwanDepartment of Surgery, Chang Gung Children's Hospital, Chang Gung University College of Medicine, Taoyuan, TaiwanBlood Systems Research Institute and Department of Laboratory Medicine, University of California, San Francisco, CA, USADepartment of Pediatrics, Chang Gung Children's Hospital, Taoyuan, TaiwanDepartment of Pediatrics, Chang Gung Children's Hospital, Taoyuan, TaiwanDepartment of Microbiology and Immunology, Graduate Institute of Basic Medical Sciences, Chang Gung University College of Medicine, Taoyuan, TaiwanIt was reported that the dose of self-antigens can determine the consequence of deletional tolerance and donor T cells are critical for tolerance induction in mixed chimeras. This study aimed at assessing the effect of cell doses and marrow T cells on engraftment and tolerance induction after prenatal bone marrow transplantation. Intraperitoneal cell transplantation was performed in FVB/N (H-2Kq) mice at gestational day 14 with escalating doses of adult C57BL/6 (H-2Kb) marrows. Peripheral chimerism was examined postnatally by flow cytometry and tolerance was tested by skin transplantation. Transplantation of light-density marrow cells showed a dose response. High-level chimerism emerged with a threshold dose of 5.0 × 106 and host leukocytes could be nearly replaced at a dose of 7.5–10.0 × 106. High-dose transplants conferred a steady long-lasting donor-specific tolerance but were accompanied by >50% incidence of graft-versus-host disease. Depletion of marrow T cells lessened graft-versus-host disease to the detriment of engraftment. With low-level chimerism, tolerance was a graded phenomenon dependent upon the level of chimerism. Durable chimerism within 6 months required a threshold of = 2% chimerism at 1 month of age and predicted a 50% chance of long-term tolerance, whereas transient chimerism (<2%) only caused hyporesponsiveness to the donor. Tolerance induction did not succeed without peripheral chimerism even if a large amount of injected donor cells persisted in the peritoneum. Neither did an increase in cell doses or donor T-cell contents benefit skin graft survivals unless it had substantially improved peripheral chimerism. Thus, peripheral chimerism level can be a simple and straightforward test to predict the degree of prenatal immune tolerance.https://doi.org/10.3727/096368908785095971 |
| spellingShingle | Jeng-Chang Chen M.D. Ming-Ling Chang Shiu-Feng Huang Pei-Yeh Chang Marcus O. Muench Ren-Huei Fu Liang-Shiou Ou Ming-Ling Kuo Prenatal Tolerance Induction: Relationship between Cell Dose, Marrow T-Cells, Chimerism, and Tolerance Cell Transplantation |
| title | Prenatal Tolerance Induction: Relationship between Cell Dose, Marrow T-Cells, Chimerism, and Tolerance |
| title_full | Prenatal Tolerance Induction: Relationship between Cell Dose, Marrow T-Cells, Chimerism, and Tolerance |
| title_fullStr | Prenatal Tolerance Induction: Relationship between Cell Dose, Marrow T-Cells, Chimerism, and Tolerance |
| title_full_unstemmed | Prenatal Tolerance Induction: Relationship between Cell Dose, Marrow T-Cells, Chimerism, and Tolerance |
| title_short | Prenatal Tolerance Induction: Relationship between Cell Dose, Marrow T-Cells, Chimerism, and Tolerance |
| title_sort | prenatal tolerance induction relationship between cell dose marrow t cells chimerism and tolerance |
| url | https://doi.org/10.3727/096368908785095971 |
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