Adaptable TCR avidity thresholds for negative selection.

نویسندگان

  • Milica Stojakovic
  • Laura I Salazar-Fontana
  • Zohreh Tatari-Calderone
  • Vladimir P Badovinac
  • Fabio R Santori
  • Damian Kovalovsky
  • Derek Sant'Angelo
  • John T Harty
  • Stanislav Vukmanovic
چکیده

Central tolerance plays a significant role in preventing autoimmune diseases by eliminating T cells with high and intermediate avidity for self. To determine the manner of setting the threshold for deletion, we created a unique transgenic mouse strain with a diverse T cell population and globally increased TCR avidity for self-peptide/MHC complexes. Despite the adaptations aimed at reducing T cell reactivity (reduced TCR levels and increased levels of TCR signaling inhibitor CD5), transgenic mice displayed more severe experimental allergic encephalomyelitis and lupus. The numbers and activity of natural (CD4(+)CD25(+)) regulatory T cells were not altered. These findings demonstrate that the threshold for deletion is adaptable, allowing survival of T cells with higher avidity when TCR avidity is globally increased.

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عنوان ژورنال:
  • Journal of immunology

دوره 181 10  شماره 

صفحات  -

تاریخ انتشار 2008