TY - JOUR
T1 - Autophagy is induced in CD4+ T cells and important for the growth factor-withdrawal cell death
AU - Li, Changyou
AU - Capan, Elizabeth
AU - Zhao, Yani
AU - Zhao, Jianping
AU - Stolz, Donna
AU - Watkins, Simon C.
AU - Jin, Shengkan
AU - Lu, Binfeng
PY - 2006/10/15
Y1 - 2006/10/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33749531942&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749531942&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.177.8.5163
DO - 10.4049/jimmunol.177.8.5163
M3 - Article
C2 - 17015701
AN - SCOPUS:33749531942
SN - 0022-1767
VL - 177
SP - 5163
EP - 5168
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -