Document 0915
 DOCN  M95A0915
 TI    Autoimmunity following neonatal tolerance to alloantigens: role of donor
       I-A and I-E molecules.
 DT    9510
 AU    Kramar G; Schurmans S; Berney M; Izui S; del Giudice G; Lambert PH;
       World Health Organization-Immunology Research and Training; Center,
       Department of Pathology, CMU, Geneva, Switzerland.
 SO    J Autoimmun. 1995 Apr;8(2):177-92. Unique Identifier : AIDSLINE
       MED/95336594
 AB    The injection of semi-allogeneic F1 spleen cells into newborn mice of a
       parental strain induces a state of immune tolerance characterized by
       anti-donor CTL unresponsiveness and the appearance of a transient
       SLE-like autoimmune syndrome associating autoantibody production,
       hypergammaglobulinemia, splenomegaly and glomerulonephritis. Our
       previous experiments have demonstrated that host Th2-like CD4+ T
       lymphocytes activate donor F1 B cells persisting in the host to produce
       autoantibodies, and that this cellular interaction relies on the
       presence of alloMHC class II molecules on donor B cells. In order to
       investigate the role and the involvement of MHC alloantigens in the
       cellular T(host)-B(donor) interaction, newborn C57BL/6 (B6) mice were
       injected with F1 spleen cells differing from the host at the level of
       defined portions of the MHC class I (K) or class II (I-A and I-E)
       molecules. B6 mice injected at birth with spleen cells from different F1
       strains were tolerant to each alloantigen (alloAg) tested, as assessed
       by specific anti-donor CTL unresponsiveness. However, the SLE-like
       autoimmune syndrome only developed in B6 mice injected at birth with F1
       spleen cells differing at the level of MHC class II I-A or I-E
       molecules. Autoantibodies appeared later in B6 mice neonatally tolerized
       to I-E alloAg than those detected in B6 mice neonatally tolerized to I-A
       alloAg. These results show that the SLE-like autoimmune disease that
       develops concomitantly to neonatally-induced tolerance to alloAg is the
       consequence of cognate T host-B donor cellular interactions triggered by
       even minute differences in the MHC class II I-A or MHC class II I-E
       molecules.
 DE    Animal  Animals, Newborn/*IMMUNOLOGY  Antibodies, Monoclonal/IMMUNOLOGY
       Antibody Specificity  *Antigen Presentation
       Autoantibodies/BIOSYNTHESIS/IMMUNOLOGY  Autoimmune
       Diseases/*IMMUNOLOGY/PATHOLOGY  B-Lymphocytes/IMMUNOLOGY  *Disease
       Models, Animal  Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
       *Genes, MHC Class II  Glomerulonephritis/ETIOLOGY  Histocompatibility
       Antigens Class II/GENETICS/*IMMUNOLOGY  Hybridization
       Hypergammaglobulinemia/ETIOLOGY  *Immune Tolerance  Immunotherapy,
       Adoptive/ADVERSE EFFECTS  Interferon Type II/BIOSYNTHESIS
       Interleukin-5/BIOSYNTHESIS  Isoantigens/ADMINISTRATION &
       DOSAGE/*IMMUNOLOGY  Lupus Erythematosus, Systemic/*IMMUNOLOGY
       *Lymphocyte Cooperation  Lymphocyte Transformation  Mice  Mice, Inbred
       C57BL  Spleen/CYTOLOGY  Support, Non-U.S. Gov't  T-Lymphocyte
       Subsets/IMMUNOLOGY  T-Lymphocytes, Cytotoxic/IMMUNOLOGY  Th2
       Cells/IMMUNOLOGY  JOURNAL ARTICLE

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