Document 0133
 DOCN  M95B0133
 TI    Intrathymic transplantation of islet antigen affects CD8+ diabetogenic
       T-cells resulting in tolerance to autoimmune IDDM.
 DT    9511
 AU    Baumann EE; Buckingham F; Herold KC; Department of Pediatrics,
       University of Chicago, Illinois 60637,; USA.
 SO    Diabetes. 1995 Aug;44(8):871-7. Unique Identifier : AIDSLINE
       MED/95347531
 AB    The acquisition of T-cell tolerance in the thymus is limited to those
       antigens expressed in the thymus at the time of T-cell development.
       Normally, islet antigens that are involved in insulin-dependent diabetes
       mellitus (IDDM) are not present in the thymus, but we have previously
       shown that transplantation of islets expressing relevant antigens into
       the thymus at the time of T-cell maturation results in prevention of
       IDDM in the multidose streptozotocin model of diabetes mellitus (MDSDM).
       Although both CD4+ and CD8+ T-cells are involved in the pathogenesis of
       this disease, the cells affected by intrathymic transplantation of
       islets are unknown. In this study, we have identified which T-cell
       subsets are affected by intrathymic islet antigens. Streptozotocin
       (STZ)-treated syngeneic islets were transplanted into the thymuses of
       C57BL/KsJ mice, and CD4+, CD8+, or both subsets of cells were
       transiently depleted with monoclonal antibodies (mAbs). After T-cell
       repopulation, animals that had received intrathymic islets followed by
       anti-CD8 mAb (P < 0.05) or both anti-CD4 and anti-CD8 mAbs (P < 0.01)
       but not anti-CD4 mAb alone were resistant to the development of
       autoimmune diabetes after five low doses of STZ. Insulitis was also
       reduced in mice receiving intrathymic islets and anti-CD8 (P < 0.025) or
       both anti-CD4 and anti-CD8 mAbs (P < 0.001).(ABSTRACT TRUNCATED AT 250
       WORDS)
 DE    Animal  Antibodies, Monoclonal/*ADMINISTRATION & DOSAGE/IMMUNOLOGY
       Antigens, CD3/ANALYSIS  CD4-Positive T-Lymphocytes/IMMUNOLOGY
       CD8-Positive T-Lymphocytes/*IMMUNOLOGY  Diabetes Mellitus,
       Experimental/*IMMUNOLOGY/PATHOLOGY  Diabetes Mellitus,
       Insulin-Dependent/*IMMUNOLOGY/PATHOLOGY  Flow Cytometry  Immune
       Tolerance  Islets of Langerhans/DRUG EFFECTS/*IMMUNOLOGY/PATHOLOGY
       Islets of Langerhans Transplantation/*IMMUNOLOGY  Lymphocyte Depletion
       Male  Mice  Mice, Inbred C57BL  Spleen/IMMUNOLOGY
       Streptozocin/PHARMACOLOGY  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       P.H.S.  T-Lymphocytes/*IMMUNOLOGY  Thymectomy  Thymus Gland
       Transplantation, Heterotopic  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).