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* Department of Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213;
University of Pittsburgh Cancer Institute, Pittsburgh, PA 15261;
Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA 15261; and
Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by Cancer Institute Investigator Award and the Pittsburgh Cancer and Aging Program Pilot Grant (to B.L.). B.L. is supported by National Institutes of Health Grant 1 K01 AR048854.
2 Address correspondence and reprint requests to Dr. Binfeng Lu, Department of Immunology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15261. E-mail address: binfeng{at}pitt.edu
3 Abbreviations used in this paper: AICD, activation-induced cell death; 3-MA, 3-methyladenine; LC3, microtubule-associated protein 1-L chain 3; RNAi, RNA inference; mTOR, mammalian target of rapamycin; TEM, transmission electron microscopy; DAPI, 4',6'-diamidino-2-phenylindole.
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