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Autophagy Is Essential for Mitochondrial Clearance in Mature T Lymphocytes¹

Heather H. Pua^*, Jian Guo^*, Masaaki Komatsu and You-Wen He^2,*

^* Department of Immunology, Duke University Medical Center, Durham, NC 27710; and PRESTO (Precursory Research for Embryonic Science and Technology), Japan Science and Technology Corporation, Kawaguchi and Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo, Japan

Macroautophagy plays an important role in the regulation of cell survival, metabolism, and the lysosomal degradation of cytoplasmic material. In the immune system, autophagy contributes to the clearance of intracellular pathogens, MHCII cross-presentation of endogenous Ags, as well as cell survival. We and others have demonstrated that autophagy occurs in T lymphocytes and contributes to the regulation of their cellular function, including survival and proliferation. Here we show that the essential autophagy gene Atg7 is required in a cell-intrinsic manner for the survival of mature primary T lymphocytes. We also find that mitochondrial content is developmentally regulated in T but not in B cells, with exit from the thymus marking a transition from high mitochondrial content in thymocytes to lower mitochondrial content in mature T cells. Macroautophagy has been proposed to play an important role in the clearance of intracellular organelles, and autophagy-deficient mature T cells fail to reduce their mitochondrial content in vivo. Consistent with alterations in mitochondrial content, autophagy-deficient T cells have increased reactive oxygen species production as well as an imbalance in pro- and antiapoptotic protein expression. With much recent interest in the possibility of autophagy-dependent developmentally programmed clearance of organelles in lens epithelial cells and erythrocytes, our data demonstrate that autophagy may have a physiologically significant role in the clearance of superfluous mitochondria in T lymphocytes as part of normal T cell homeostasis.

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 by National Institutes of Health Grant AI-073947.

² Address correspondence and reprint requests to Dr. You-Wen He, Department of Immunology, Duke University Medical Center, Box 3010, Durham, NC 27710. E-mail address: he000004{at}mc.duke.edu

³ Abbreviations used in this paper: LN, lymph node; AIF, apoptosis-inducing factor; DN, double negative; DP, double positive; MFI, mean fluorescence intensity; ROS, reactive oxygen species; SP, single positive.

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