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.[1]References
- Involvement of MKK6 in TCRalphabeta(int)CD69lo: a target population for apoptotic cell death in thymocytes. Suzuki, H., Wu, J., Hossain, K., Ohhata, T., Du, J., Akhand, A.A., Hayakawa, A., Kimura, H., Hagiwara, M., Nakashima, I. FASEB J. (2003) [Pubmed]
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