A positively selecting thymic epithelial cell line lacks costimulatory activity

Stanislav Vukmanović, Greg Stella, Philip D. King, Rubendra Dyall, Kristin A. Hogquist, John T. Harty, Janko Nikolić-Žugić, Michael J. Bevan

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25 Scopus citations

Abstract

The participation of costimulatory molecule interactions in positive selection of T lymphocytes was addressed by assessing the ability of a positively selecting thymic epithelial cell (TEC) line, 427.1, to stimulate allospecific CTL responses. Stimulation of H-2(s) spleen cells with the H- 2b expressing 427.1 line does not result in the generation of cells capable of lysing H-2b target cell lines. The level of expression of MHC class I molecules by 427.1 is lower than that found in other stimulatory TEC lines. However, this finding does not account for the nonstimulatory phenotype. Up- regulation of MHC class I did not result in stimulation, and fusion of 427.1 cells with stimulatory TEC resulted in a line with low MHC class I molecule expression and stimulatory phenotype. The TEC line 427.1 does not express the costimulatory molecule B7/BB1, and transfection of the B7/BB1-encoding DNA results in expression of the molecule and conversion into a stimulatory phenotype, demonstrating directly that the non-stimulatory phenotype is a result of lack of costimulation. However, B7/BB1 expression does not improve the ability of 427.1 TECs to induce positive selection. Intrathymic injection of the B7/BB1 transfected, compared with mock transfected 427.1 cells, rescued fewer CD8+ mature thymocytes in β2-microglobulin negative mice. Therefore, unlike the peripheral T cell responses to Ag, positive selection of T cells in the thymus may not depend on the costimulation provided by the presenting cell.

Original languageEnglish (US)
Pages (from-to)3814-3823
Number of pages10
JournalJournal of Immunology
Volume152
Issue number8
StatePublished - Apr 15 1994
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Vukmanović, S., Stella, G., King, P. D., Dyall, R., Hogquist, K. A., Harty, J. T., Nikolić-Žugić, J., & Bevan, M. J. (1994). A positively selecting thymic epithelial cell line lacks costimulatory activity. Journal of Immunology, 152(8), 3814-3823.