A thymic epithelial cell line induces both positive and negative selection in the thymus

Stanislav Vukmanović, Stephen C. Jameson, Michael J. Bevan

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

TCR engagement in the thymus results in both survival and elimination signals for developing thymocytes. To examine whether both signals can be provided by the same cell type, we investigated the ability of a thymic epithelial cell (TEC) line 427.1, previously shown to allow positive selection in the thymus, to induce clonal deletion of Immature thymocytes. [H-2b/s-H-2s] bone marrow chimeras are non-responsive to antigens in the context of H-2b. However, chimeras that underwent intrathymic injection of H-2b/s 427.1 cells expressing vesicular stomatitis virus (VSV) nucleocapsid antigen acquired the ability to raise influenza, but not VSV specific H-2b restricted cytotoxic T lymphocyte (CTL) responses. The ability of 427.1 cells to delete CD4+CD8+ thymocytes was determined using mice transgenlc for the TCR specific for ovalbumln (OVA) in the context of H-2Kb. OVA transfected, but not mock transfected 427.1 TECs, Induced in vitro deletion of CD4+CD8+ TCR transgenlc thymocytes manifested as a down-modulation of CD4 and CD8 molecules, a shift in the side versus forward scatter characteristics of thymocytes, and appearance of thymocytes with subdlplold content of DNA indicated the ongoing process of DNA fragmentation. The finding that the same TEC line Is capable of inducing both positive and negative selection in the thymus suggests that thymocytes bearing TCRs specific for self peptldes expressed by positively selecting thymic epithelium can be deleted. Therefore the expression of a unique set of MHC associated peptldes by TECs does not appear to be the basis for the positive outcome of the TCR llgatlon on immature thymocytes.

Original languageEnglish (US)
Pages (from-to)239-246
Number of pages8
JournalInternational Immunology
Volume6
Issue number2
DOIs
StatePublished - Feb 1 1994

Keywords

  • Clonal deletion
  • Cytotoxic T cells
  • Selection
  • Thymus

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