International Immunology, Vol 10, 767-774, Copyright © 1998 by Oxford University Press
Y Ghendler, E Mizoguchi, AK Bhan and LK Clayton
Thymocytes bearing autoreactive TCR are eliminated from the organism by a
process termed negative selection. The molecular basis of this deletion has
been recently shown to be a consequence of TCR-triggered activation of a
caspase by certain peptide-MHC ligands in the immature CD4+CD8+
double-positive (DP) thymocyte subpopulation. Of note, the numerically
minor TCRhigh DP thymocyte subpopulation, unlike the major TCRlow DP
subset, is resistant to negative selection. Despite exposure to cognate
peptide, TCRhigh DP thymocytes mature into single-positive thymocytes and
are exported into the periphery. Here we investigated the mechanism by
which these thymocytes escape negative selection. Using a cytochemical
assay in conjunction with a caspase-specific affinity ligand, we
demonstrate that the resistance of the TCRhigh DP thymocytes to negative
selection correlates with the disappearance of TCR-triggered caspase
activity in these cells. Thus thymocytes which have presumably begun the
positive selection process inactivate the thymic caspase pathway and are no
longer susceptible to negative selection.
ARTICLES
Double-positive thymocytes resistant to antigen-MHC-induced negative selection lack active caspase
Laboratory of Immunology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
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