       Document 0171
 DOCN  M95B0171
 TI    Quantitative analysis of the efficiency of clonal deletion in the
       thymus.
 DT    9511
 AU    Spain LM; Berg LJ; Department of Cellular and Developmental Biology,
       Harvard; University, Cambridge, Massachusetts 02138, USA.
 SO    Dev Immunol. 1994;4(1):43-53. Unique Identifier : AIDSLINE MED/95345689
 AB    One of the major mechanisms for establishing self-tolerance is the
       clonal deletion of self-reactive T cells during their development in the
       thymus. Using a TCR transgenic mouse model, we have established a
       quantitative ex vivo assay for examining the sensitivity and specificity
       of negative selection. Thymic organ cultures established from mice of
       varying MHC haplotypes were incubated with antigen, and the efficiency
       of clonal deletion assessed. We show here that clonal deletion of CD4+8+
       thymocytes is sensitive to both the gene dosage and the allelic
       variation of MHC class II molecules expressed on thymic
       antigen-presenting cells. We also find that when epithelial cells in the
       thymic cortex are the only antigen-presenting cells expressing the
       appropriate MHC class II molecules, negative selection of CD4+8+ cells
       is as efficient as when antigen is presented on all thymic
       antigen-presenting cells. These studies demonstrate that the induction
       of self-tolerance via clonal deletion in the thymus is a function not
       only of antigen concentration, but also of MHC class II cell-surface
       density. In addition, together with the reports of others, these results
       confirm that cortical epithelial cells can mediate negative selection,
       and demonstrate that they do so in the intact thymic microenvironment.
 DE    Animal  Clone Cells/IMMUNOLOGY  CD4-CD8 Ratio  Gene Deletion  Haplotypes
       Major Histocompatibility Complex/GENETICS/*IMMUNOLOGY  Mice  Mice,
       Transgenic  Organ Culture  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       P.H.S.  T-Lymphocytes/*IMMUNOLOGY  Thymus Gland/*EMBRYOLOGY/IMMUNOLOGY
       JOURNAL ARTICLE

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

