[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.