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.
Li
Changyou
C
Department of Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Capan
Elizabeth
E
Zhao
Yani
Y
Zhao
Jianping
J
Stolz
Donna
D
Watkins
Simon C
SC
Jin
Shengkan
S
Lu
Binfeng
B
D000818:Animals; D017209:Apoptosis; D001343:Autophagy / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D006706:Homeostasis; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D015398:Signal Transduction; D018418:Th2 Cells
D036341:Intercellular Signaling Peptides and Proteins