Autophagy Is Induced in CD4+ T Cells and Important for the Growth Factor-Withdrawal Cell Death.
Autophagy is a tightly regulated catabolic mechanism that degrades proteins and organelles. Autophagy mediates programmed cell death under certain conditions. To determine the role of autophagy in T cells, we examined, in mouse CD4(+) T cells, conditions under which autophagy is induced and alterations of the cell fate when autophagy is blocked. We have found that resting naive CD4(+) T cells do not contain detectable autophagosomes. Autophagy can be observed in activated CD4(+) T cells upon TCR stimulation, cytokine culturing, and prolonged serum starvation. Induction of autophagy in T cells requires JNK and the class III PI3K. Autophagy is inhibited by caspases and mammalian target of rapamycin in T cells. Interestingly, more Th2 cells than Th1 cells undergo autophagy. Th2 cells become more resistant to growth factor-withdrawal cell death when autophagy is blocked using either chemical inhibitors 3-methyladenine, or by RNA interference knockdown of beclin 1 and Atg7. Therefore, autophagy is an important mechanism that controls homeostasis of CD4(+) T cells.[1]References
- Autophagy Is Induced in CD4+ T Cells and Important for the Growth Factor-Withdrawal Cell Death. Li, C., Capan, E., Zhao, Y., Zhao, J., Stolz, D., Watkins, S.C., Jin, S., Lu, B. J. Immunol. (2006) [Pubmed]
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