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.
Suzuki
Haruhiko
H
Department of Immunology, Nagoya University Graduate School of Medicine, Aichi 466-8550, Japan. k46200a@nucc.cc.nagoya-u.ac.jp
Wu
Jianghong
J
Hossain
Khaled
K
Ohhata
Tatsuya
T
Du
Jun
J
Akhand
Anwarul A
AA
Hayakawa
Akemi
A
Kimura
Hiroshi
H
Hagiwara
Masatoshi
M
Nakashima
Izumi
I
D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D017209:Apoptosis; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000502:physiology*; D037181:Lectins, C-Type; D048669:MAP Kinase Kinase 6; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D037181:Lectins, C-Type; D048669:MAP Kinase Kinase 6; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000099192:CD69 Antigens; C482567:Map2k6 protein, mouse