Allogeneic chimerism with low-dose irradiation, antigen presensitization, and costimulator blockade in H-2 mismatched mice
| Autor: | Han Wang, Peter J. Quesenberry, F. Marc Stewart, Suju Zhong |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
Time Factors medicine.drug_class Cell Transplantation Immunology CD40 Ligand Graft vs Host Disease Spleen Monoclonal antibody Biochemistry Immunophenotyping Mice Antigen medicine Immune Tolerance Animals Transplantation Homologous Bone Marrow Transplantation Transplantation Chimera CD40 biology Dose-Response Relationship Drug Graft Survival H-2 Antigens Antibodies Monoclonal Cell Biology Hematology Histocompatibility Transplantation medicine.anatomical_structure Blood Group Incompatibility Models Animal biology.protein Immunization Bone marrow Stem cell Whole-Body Irradiation |
| Zdroj: | Blood. 97(2) |
| ISSN: | 0006-4971 |
| Popis: | We have previously shown that the keys to high-level nontoxic chimerism in syngeneic models are stem cell toxic, nonmyelotoxic host treatment as provided by 100-cGy whole-body irradiation and relatively high levels of marrow stem cells. This approach was unsuccessful in H-2 mismatched B6.SJL to BALB/c marrow transplants, but with tolerization, stable multilineage chimerism was obtained. Ten million B6.SJL spleen cells were infused intravenously into BALB/c hosts on day −10 and (MR-1) anti-CD40 ligand monoclonal antibody (mAb) injected intraperitoneally at varying levels on days −10, −7, −3, 0, and +3 and the BALB/c mice irradiated (100 cGy) and infused with 40 million B6.SJL/H-2 mismatched marrow cells on day 0. Stable multilineage chimerism at levels between 30% to 40% was achieved in the great majority of mice at 1.6 mg anti-CD40 ligand mAb per injection out to 64 weeks after transplantation, without graft-versus-host disease. The transplanted mice were also tolerant of donor B6.SJL, but not third-party CBA/J skin grafts at 8 to 9 and 39 to 43 weeks after marrow transplantation. These data provide a unique model for obtaining stable partial chimerism in H-2 mismatched mice, which can be applied to various clinical diseases of man such as sickle cell anemia, thalassemia, and autoimmune disorders. |
| Databáze: | OpenAIRE |
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