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


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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@article{Suzuki2003InvolvementOM, title={Involvement of MKK6 in TCRalphabeta(int)CD69lo: a target population for apoptotic cell death in thymocytes.}, author={Haruhiko Suzuki and Jianghong Wu and Khaled Hossain and Tatsuya Ohhata and Jun Du and Anwarul Azim Akhand and Akemi Hayakawa and Hiroshi Kimura and Masatoshi Hagiwara and Izumi Nakashima}, journal={FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, year={2003}, volume={17 11}, pages={1538-40} }