Résumé :
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Communication n° 139 Introduction : Our Myoblast Allotransplantation Studies In Monkeys Showed That The Absence Of Immunosuppression Leads To Graft Rejection In A Few Days, While A Good Immunosuppression Allows Graft Survival Apparently As Long As Desired. However, We Observed Focal Lymphocyte Accumulations In Skeletal Muscles That Received Myoblast Allotransplantations, Both In Some Immunosuppressed Muscular-Dystrophy Patients And In Monkeys Treated With Tacrolimus At Moderate Dosages. This Raises The Question Of Whether This Histological Presentation Of Myositis Corresponds To Non-Completely Controlled Acute Rejection Noxious To The Graft. Objective : To Study The Immune Cellular Reactions And The Graft Survival In Skeletal Muscles Of Monkeys After Myoblast Allotransplantation And During Tacrolimus Immunosuppression Maintaining Blood Levels Near Those Used In Human Transplantation. Methods : Four Cynomolgus Monkeys Received Allotransplantations Of ß-Galactosidase-Labeled Myoblasts In The Biceps Brachii Following Our High-Density Injection Protocol. They Received Tacrolimus For Immunosuppression, Targeting Blood Levels Between 10 And 30 Ng/Ml. The Myoblast-Injected Muscles Were Biopsied At 1, 3 And 5 Months After Transplantation. Cryostat Sections Of The Biopsies Were Histologically Analyzed. The Presence Of Antibodies Against The Donor Myoblasts Was Tested. Results : All Biopsies Showed Abundant ß-Galactosidase-Positive Myofibers 1 Month Post-Transplantation, Together With Focal Dense Leukocyte Accumulations. The Percentage Of ß-Galactosidase-Positive Myofibers Decreased Progressively Until Total Or Almost Total Disappearance At 3 And 5 Months, The Leukocyte Accumulations Being Always Present. These Leukocyte Accumulations Were Composed Mainly By Macrophages And Cd8+ And Cd4+ Lymphocytes. A Lower Percentage Of Eosinophils Was Observed. Mhc-Class I Expression Was Observed In Hybrid Myofibers. All Monkeys Developed Antibodies Against The Donor Myoblasts. Conclusions : In Primates That Received Myoblast-Allotransplantation Under Immunosuppression, A Myositis Characterized By Focal Dense Accumulations Of Lymphocytes And Macrophages, Is The Expression Of A Non-Completely Controlled Acute Rejection That Can Insidiously Lyse The Hybrid Myofibers Until Their Elimination.
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