FasL-induced downregulation of CD28 expression on jurkat cells in vitro is associated with activation of caspases.
Ligation of CD28, which is present on the majority of CD4(+)T cells, promotes proliferation and immune responses. However, expression of CD28 declines with aging, and apoptosis may contribute to this decline. We have investigated the molecular mechanism underlying the decrease in CD28 expression in Jurkat T cells cultured with FasL. FasL blocks expression of CD28 at the transcriptional level. This correlates with activation of caspase cascades: active caspase-3 can be detected and inhibitors of caspase-3 and caspase-8 increase CD28 promoter activity and CD28 expression. These findings are consistent with the hypothesis that apoptosis plays a key role in the age-related decline of CD28 expression and hence in immunosenescence.
Ma
Shibin
S
Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
Ochi
Hirotomo
H
Cui
Lianxian
L
He
Wei
W
D020121:5' Untranslated Regions; D000375:Aging; D017302:Annexins / Q000494:pharmacology; D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D018106:CD28 Antigens / Q000096:biosynthesis* / Q000235:genetics; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D016922:Cellular Senescence; D003001:Cloning, Molecular; D004396:Coloring Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004789:Enzyme Activation; D053222:Fas Ligand Protein; D017930:Genes, Reporter; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D008156:Luciferases / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008954:Models, Biological; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014158:Transcription, Genetic
D020121:5' Untranslated Regions; D017302:Annexins; D018106:CD28 Antigens; D017252:CD3 Complex; D016827:CD8 Antigens; D004396:Coloring Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D008156:Luciferases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C022616:thiazolyl blue