Document 0996
 DOCN  M9540996
 TI    Tolerance induction by elimination of subsets of self-reactive
       thymocytes.
 DT    9504
 AU    Sponaas AM; Tomlinson PD; Schulz R; Antoniou J; Ize-Iyamu P;
       Schmitt-Verhulst AM; Mellor AL; Division of Molecular Immunology,
       National Institute for Medical; Research, Mill Hill, London, UK.
 SO    Int Immunol. 1994 Oct;6(10):1593-604. Unique Identifier : AIDSLINE
       MED/95127563
 AB    Immature thymocytes expressing TCRs which confer reactivity to self-MHC
       molecules are subject to efficient elimination as a result of negative
       selection. Previously, we have identified a lineage of H-2Kb Tg mice,
       CD2Kb-3, which fails to reject skin grafts from mice expressing H-2Kb
       even though H-2Kb-specific cytotoxic T cells can be generated in vitro.
       We now show that bone marrow derived cells are responsible for tolerance
       induction and that tolerance is acquired, at least in part, by negative
       selection in CD2Kb-3 mice. Thymocytes expressing two different
       transgenic TCR (TCR-Tg) clonotypes conferring reactivity to H-2Kb are
       eliminated prior to the CD8+CD4+ stage of differentiation in double Tg
       (CD2Kb-3 x TCR-Tg)F1 mice. As in other cases where thymocytes from
       TCR-Tg mice develop in the presence of deleting ligands, large numbers
       of TCR+ CD8-CD4- T cells accumulate in double Tg mice. However, these T
       cells fail to respond to H-2Kb in vitro but can be activated with
       immobilized anti-clonotypic antibody. Consequently, thymocytes
       expressing these types of TCR molecules represent a fraction of
       H-2Kb-reactive thymocytes which are unable to mature into T cells
       capable of mounting H-2Kb-specific cytotoxic responses. Presumably,
       precursors of H-2Kb-specific cytotoxic T cells found in the periphery of
       CD2Kb-3 mice express a distinct repertoire of TCR molecules conferring
       reactivity to H-2Kb. We consider potential explanations to account for
       this discrepancy and their wider implications, including the possibility
       that the repertoire of thymocytes able to recognize self-H-2Kb molecules
       in CD2Kb-3 mice is divided into distinct subsets; those which are, and
       those which are not, subject to negative selection.
 DE    Animal  Bone Marrow Transplantation/IMMUNOLOGY  Cell
       Differentiation/IMMUNOLOGY  Clonal Deletion/*IMMUNOLOGY  Cytotoxicity
       Tests, Immunologic  CD4-Positive T-Lymphocytes/IMMUNOLOGY  CD8-Positive
       T-Lymphocytes/IMMUNOLOGY  Enzyme-Linked Immunosorbent Assay  Flow
       Cytometry  H-2 Antigens/BIOSYNTHESIS  Lymphocyte Culture Test, Mixed
       Lymphocyte Transformation  Mice  Mice, Inbred BALB C  Mice, Inbred CBA
       Receptors, Antigen, T-Cell/*BIOSYNTHESIS  Skin
       Transplantation/IMMUNOLOGY  Support, Non-U.S. Gov't
       T-Lymphocytes/*CYTOLOGY  Thymus Gland/*CYTOLOGY  JOURNAL ARTICLE

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