[Regulation of thymocyte apoptosis and positive selection].
Developing T cells undergo thymic selection at the CD4+CD8+ stage. Only less than 5% of CD4+CD8+ thymocytes are positively selected to survive and differentiate into mature single positive CD4 or CD8 T cells. Positive selection requires signaling through the T cell receptors (TCR) with assistance of CD4 or CD8 coreceptor and LFA-1, but its molecular mechanism is poorly understood. By using glucocorticoids, anti-apoptotic activity was detected in CD4+CD8+ thymocytes upon proper cross-linking of TCR/CD3 complex with CD4, CD8, or LFA-1, and was mimicked by a combination of a calcium ionophore and a protein kinase C activator. Isolated CD4+CD8+ thymocytes underwent differentiation and commitment to the CD4 T cell lineage by moderate and transient stimulation with this combination of the drugs.
Iwata
M
M
Mitsubishi Kasei Institute of Life Sciences, Project Research Center.
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins; D006801:Humans; D015759:Ionomycin; D010749:Phosphoprotein Phosphatases; D011493:Protein Kinase C; D015398:Signal Transduction; D013950:Thymus Gland / Q000166:cytology*
D002148:Calmodulin-Binding Proteins; D015759:Ionomycin; D011493:Protein Kinase C; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases