Minor Antigen Disparities Impede Induction of Long Lasting Chimerism and Tolerance through Bone Marrow Transplantation with Costimulation Blockade
Mixed chimerism and tolerance can be successfully induced in rodents through allogeneic bone marrow transplantation (BMT) with costimulation blockade (CB), but varying success rates have been reported with distinct models and protocols. We therefore investigated the impact of minor antigen dispariti...
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| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2016/8635721 |
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| author | Sinda Bigenzahn Ines Pree Christoph Klaus Nina Pilat Benedikt Mahr Elisabeth Schwaiger Patrick Nierlich Friedrich Wrba Thomas Wekerle |
| author_facet | Sinda Bigenzahn Ines Pree Christoph Klaus Nina Pilat Benedikt Mahr Elisabeth Schwaiger Patrick Nierlich Friedrich Wrba Thomas Wekerle |
| author_sort | Sinda Bigenzahn |
| collection | DOAJ |
| description | Mixed chimerism and tolerance can be successfully induced in rodents through allogeneic bone marrow transplantation (BMT) with costimulation blockade (CB), but varying success rates have been reported with distinct models and protocols. We therefore investigated the impact of minor antigen disparities on the induction of mixed chimerism and tolerance. C57BL/6 (H2b) mice received nonmyeloablative total body irradiation (3 Gy), costimulation blockade (anti-CD40L mAb and CTLA4Ig), and 2×107 bone marrow cells (BMC) from either of three donor strains: Balb/c (H2d) (MHC plus multiple minor histocompatibility antigen (mHAg) mismatched), B10.D2 (H2d) or B10.A (H2a) (both MHC mismatched, but mHAg matched). Macrochimerism was followed over time by flow cytometry and tolerance was tested by skin grafting. 20 of 21 recipients of B10.D2 BMC but only 13 of 18 of Balb/c BMC and 13 of 20 of B10.A BMC developed stable long-term multilineage chimerism (p<0.05 for each donor strain versus B10.D2). Significantly superior donor skin graft survival was observed in successfully established long-term chimeras after mHAg matched BMT compared to mHAg mismatched BMT (p<0.05). Both minor and major antigen disparities pose a substantial barrier for the induction of chimerism while the maintenance of tolerance after nonmyeloablative BMT and costimulation blockade is negatively influenced by minor antigen disparities. |
| format | Article |
| id | doaj-art-3ec33d2db81c48fca68600e03e2789f0 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-3ec33d2db81c48fca68600e03e2789f02025-02-03T05:59:50ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/86357218635721Minor Antigen Disparities Impede Induction of Long Lasting Chimerism and Tolerance through Bone Marrow Transplantation with Costimulation BlockadeSinda Bigenzahn0Ines Pree1Christoph Klaus2Nina Pilat3Benedikt Mahr4Elisabeth Schwaiger5Patrick Nierlich6Friedrich Wrba7Thomas Wekerle8Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18, 1090 Vienna, AustriaSection of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18, 1090 Vienna, AustriaSection of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18, 1090 Vienna, AustriaSection of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18, 1090 Vienna, AustriaSection of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18, 1090 Vienna, AustriaSection of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18, 1090 Vienna, AustriaSection of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18, 1090 Vienna, AustriaInstitute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18, 1090 Vienna, AustriaSection of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18, 1090 Vienna, AustriaMixed chimerism and tolerance can be successfully induced in rodents through allogeneic bone marrow transplantation (BMT) with costimulation blockade (CB), but varying success rates have been reported with distinct models and protocols. We therefore investigated the impact of minor antigen disparities on the induction of mixed chimerism and tolerance. C57BL/6 (H2b) mice received nonmyeloablative total body irradiation (3 Gy), costimulation blockade (anti-CD40L mAb and CTLA4Ig), and 2×107 bone marrow cells (BMC) from either of three donor strains: Balb/c (H2d) (MHC plus multiple minor histocompatibility antigen (mHAg) mismatched), B10.D2 (H2d) or B10.A (H2a) (both MHC mismatched, but mHAg matched). Macrochimerism was followed over time by flow cytometry and tolerance was tested by skin grafting. 20 of 21 recipients of B10.D2 BMC but only 13 of 18 of Balb/c BMC and 13 of 20 of B10.A BMC developed stable long-term multilineage chimerism (p<0.05 for each donor strain versus B10.D2). Significantly superior donor skin graft survival was observed in successfully established long-term chimeras after mHAg matched BMT compared to mHAg mismatched BMT (p<0.05). Both minor and major antigen disparities pose a substantial barrier for the induction of chimerism while the maintenance of tolerance after nonmyeloablative BMT and costimulation blockade is negatively influenced by minor antigen disparities.http://dx.doi.org/10.1155/2016/8635721 |
| spellingShingle | Sinda Bigenzahn Ines Pree Christoph Klaus Nina Pilat Benedikt Mahr Elisabeth Schwaiger Patrick Nierlich Friedrich Wrba Thomas Wekerle Minor Antigen Disparities Impede Induction of Long Lasting Chimerism and Tolerance through Bone Marrow Transplantation with Costimulation Blockade Journal of Immunology Research |
| title | Minor Antigen Disparities Impede Induction of Long Lasting Chimerism and Tolerance through Bone Marrow Transplantation with Costimulation Blockade |
| title_full | Minor Antigen Disparities Impede Induction of Long Lasting Chimerism and Tolerance through Bone Marrow Transplantation with Costimulation Blockade |
| title_fullStr | Minor Antigen Disparities Impede Induction of Long Lasting Chimerism and Tolerance through Bone Marrow Transplantation with Costimulation Blockade |
| title_full_unstemmed | Minor Antigen Disparities Impede Induction of Long Lasting Chimerism and Tolerance through Bone Marrow Transplantation with Costimulation Blockade |
| title_short | Minor Antigen Disparities Impede Induction of Long Lasting Chimerism and Tolerance through Bone Marrow Transplantation with Costimulation Blockade |
| title_sort | minor antigen disparities impede induction of long lasting chimerism and tolerance through bone marrow transplantation with costimulation blockade |
| url | http://dx.doi.org/10.1155/2016/8635721 |
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