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Publication : Involvement of MKK6 in TCRalphabeta(int)CD69lo: a target population for apoptotic cell death in thymocytes.

First Author  Suzuki H Year  2003
Journal  FASEB J Volume  17
Issue  11 Pages  1538-40
PubMed ID  12824301 Mgi Jnum  J:100093
Mgi Id  MGI:3586937 Doi  10.1096/fj.02-0869fje
Citation  Suzuki H, et al. (2003) Involvement of MKK6 in TCRalphabeta(int)CD69lo: a target population for apoptotic cell death in thymocytes. FASEB J 17(11):1538-40
abstractText  By analyzing real-time caspase activity and DNA fragmentation in live thymocytes, we found that apoptosis occurs predominantly in a TCRalphabeta(int)/hiCD69lo population. The number of caspase-active cells and DNA-fragmented cells in MKK6-deficient mice, which were originally generated in our laboratory by gene targeting, was decreased in the TCRalphabeta(int)CD69lo population but not in the TCRalphabetahiCD69lo population. The percentage of caspase-active cells in the H-Y-specific TCRint population was more clearly decreased in male MKK6-deficient H-Y TCR-transgenic mice. Furthermore, the absolute number of TCRhiCD4loCD8lo cells, which are developmentally next to TCRintCD4hiCD8hi cells, was increased in MKK6-deficient H-Y TCR-transgenic mice. Deletion of TCRalphabeta(int)CD4hiCD8hi cells by injecting antigenic lymphocytic chorio-meningitis virus (LCMV) peptide into LCMV-specific TCR-transgenic mice was incomplete in MKK6-deficient mice. Cellular death of TCRalphabeta(int) fetal thymocytes induced by adding an antigenic peptide into an in vitro fetal thymic organ culture system was also diminished in MKK6-deficient TCR-transgenic thymi. These results indicate that MKK6 plays a role in the developing thymocytes, especially in the population of TCRalphabeta(int)CD69lo cells, which possibly undergo negative selection.
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