Leukemia prevention and long-term survival of AKR mice transplanted with MHC-matched or MHC-mismatched bone marrow |
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| Authors: | R E Longley R A Good |
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| Affiliation: | 1. Department of Biological Sciences, University of Central Florida, Orlando, 32816 USA;2. Department of Pediatrics, All Childrens''Hospital, St. Petersburg, Florida 33701 USA;1. Department of Pediatrics, Abramson Research Center, Children’s Hospital of Philadelphia Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania;2. Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;3. Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania;4. Center for Neuroscience at the University of Pittsburgh, Pittsburgh, Pennsylvania;5. Center for Applied Genomics, Abramson Research Center, Children’s Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania;6. Department of Physiology, University of Melbourne, Parkville, Victoria, Australia;7. Department of Dermatology, University of Florida, Gainesville, Florida;8. Department of Neurosciences, University of Toledo Health Sciences Campus, Toledo, Ohio;1. Medical Clinic 1, Friedrich-Alexander-University, Erlangen, Germany;2. Institute of Clinical Physiology, Charité–Universitätsmedizin Berlin, Berlin, Germany;3. Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité–Universitätsmedizin Berlin, Berlin, Germany;1. Epigenetics and Diabetes Unit, Department of Clinical Sciences Malmö, Lund University Diabetes Centre, Scania University Hospital, Malmö, Sweden;1. Department of Surgery, Duke Center for Human Systems Immunology, Durham, NC, USA;2. Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA;3. Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA;4. Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA |
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| Abstract: | The current studies were designed to evaluate the effectiveness of marrow transplantation within and outside the major histocompatibility complex (MHC) on the long-term survival and occurrence of spontaneous leukemia in AKR mice. AKR mice, which were lethally irradiated and received MHC-matched marrow from CBA/J mice (CBA----AKR), never developed leukemia and were alive and remained healthy for up to 280 days post-transplant. These long-term surviving chimeras possessed substantial immune vigor when both cell-mediated and humoral responses were tested. Lethally irradiated AKR mice, which had received MHC-mismatched marrow (anti-Thy-1.2 treated or nontreated) from C57BL/6J mice (B6----AKR), never developed leukemia and survived up to 170 days post-transplant. However, both groups of these chimeras began dying 180 to 270 days post-transplant due to a disease process which could not be readily identified. Histological analysis of B6----AKR chimeras revealed severe lymphoid cell depletion in thymus and spleen; however, none of these chimeras exhibited classical features of acute graft versus host disease. Concanavalin A mitogenesis, primary antibody responses to sheep red blood cells and the production of interleukin 2 (IL-2) were suppressed in B6----AKR chimeras. IL-2 treatment of B6----AKR chimeras was shown to partially correct these deficiencies without stimulating mixed lymphocyte responsiveness to donor or host lymphocytes. These studies indicate that the use of MHC-mismatched marrow for the prevention of spontaneous AKR leukemia may rely on augmentative IL-2 therapy for complete immune reconstitution of leukemia-free chimeras. |
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