Influence of dimethyl myleran on tolerance induction and immune function in major histocompatibility complex-haploidentical murine bone-marrow transplantation
| Autor: | Eizaburo Ishii, Nazareth Gengozian, Robert A. Good |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Cytotoxicity
Immunologic medicine.medical_treatment Population Mice Inbred Strains Biology Major Histocompatibility Complex Mice Immune Tolerance medicine Animals education Busulfan Bone Marrow Transplantation Immunity Cellular education.field_of_study Multidisciplinary Immunosuppression Total body irradiation Mixed lymphocyte reaction Transplantation Tolerance induction medicine.anatomical_structure Radiation Chimera Antibody Formation Immunology Bone marrow Lymphocyte Culture Test Mixed Research Article medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 88:8435-8439 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | To study murine major histocompatibility complex (MHC)-haploidentical bone-marrow transplantation (BMT), B6C3F1 mice (H-2b/k) underwent BMT using syngeneic [B6C3F1 (H-2b/k)], haploidentical [CB6F1 (H-2d/b)], or fully allogeneic [DBA/2 (H-2d)] donor mice. As pretreatment, dimethyl myleran (DMM), an alkylating agent that produces effective myeloablation but little immunosuppression, was used with total body irradiation (TBI). Four conditioning regimens were studied: TBI 800 rads (1 rad = 0.01 Gy), TBI 950 rads, TBI 800 rads plus DMM (0.2 mg per mouse), and TBI 950 rads plus DMM. Survival rates, chimerism, proliferative responses in mixed-lymphocyte culture, specific cell-mediated lympholysis, and in vivo plaque-forming cell responses to several antigens were compared. TBI 800 rads plus DMM was maximally effective. Haploidentical BMT was as successful in inducing long-term survival and immune and hematologic reconstitution as was syngeneic BMT. This regimen plus haploidentical BMT of T-cell-purged marrow yielded survivors tolerant of donor and recipient major histocompatibility complex. Such myeloablation and immunosuppression prevented graft rejection, immunodeficiency due to histoincompatibility, and damage to a radiosensitive cell population. A microenvironmental influence crucial to some antibody responses was thus revealed. Delayed recovery of antibody production after BMT in humans may be due partly to suboptimal myeloablation or excess irradiation. |
| Databáze: | OpenAIRE |
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