Skip to main content

Autophagy and T Cell Aging

  • Living reference work entry
  • First Online:
Handbook of Immunosenescence
  • 184 Accesses

Abstract

Autophagy involves the degradation and recycling of cytosolic material in the lysosomes. At least three general forms of autophagy, macroautophagy, microautophagy, and chaperon-mediated autophagy, have been described in mammalian cells and are defined by the mechanisms utilized by cytosolic components to reach the lysosomal lumen. Autophagy plays a central role in a wide array of cellular functions that range from the maintenance of cell homeostasis and quality control to the modulation of the response to stress or the regulation of programs of cell activation and differentiation. A decline in the activity of different forms of autophagy with age has been described in many cells types and tissues, including cells of the immune system. This chapter will provide an overview of the role that different forms of autophagy play in the regulation of the T cell response and will analyze how a dysregulation of those forms of autophagy may underlie the functional defects that characterize T cell responses in old organisms.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  • Arias E, Koga H, Diaz A, Mocholi E, Patel B, Cuervo AM (2015) Lysosomal mTORC2/PHLPP1/Akt regulate chaperone-mediated autophagy. Mol Cell 59(2):270–284

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Arnold CR, Pritz T, Brunner S, Knabb C, Salvenmoser W, Holzwarth B, Thedieck K, Grubeck-Loebenstein B (2014) T cell receptor-mediated activation is a potent inducer of macroautophagy in human CD8(+)CD28(+) T cells but not in CD8(+)CD28(−) T cells. Exp Gerontol 54:75–83

    Article  CAS  PubMed  Google Scholar 

  • Bandyopadhyay U, Kaushik S, Varticovski L, Cuervo AM (2008) The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane. Mol Cell Biol 28(18):5747–5763

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bandyopadhyay U, Sridhar S, Kaushik S, Kiffin R, Cuervo AM (2010) Identification of regulators of chaperone-mediated autophagy. Mol Cell 39(4):535–547

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Botbol Y, Patel B, Macian F (2015) Common gamma-chain cytokine signaling is required for macroautophagy induction during CD4+ T-cell activation. Autophagy 11(10):1864–1877

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Botbol Y, Guerrero-Ros I, Macian F (2016) Key roles of autophagy in regulating T-cell function. Eur J Immunol 46(6):1326–1334

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Boucher N, Dufeu-Duchesne T, Vicaut E, Farge D, Effros RB, Schachter F (1998) CD28 expression in T cell aging and human longevity. Exp Gerontol 33(3):267–282

    Article  CAS  PubMed  Google Scholar 

  • Chen M, Hong MJ, Sun H, Wang L, Shi X, Gilbert BE, Corry DB, Kheradmand F, Wang J (2014) Essential role for autophagy in the maintenance of immunological memory against influenza infection. Nat Med 20(5):503–510

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cuervo AM (2008) Autophagy and aging: keeping that old broom working. Trends Genet 24(12):604–612

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cuervo AM, Dice JF (1996) A receptor for the selective uptake and degradation of proteins by lysosomes. Science 273(5274):501–503

    Article  CAS  PubMed  Google Scholar 

  • Cuervo AM, Macian F (2014) Autophagy and the immune function in aging. Curr Opin Immunol 29:97–104

    Article  CAS  PubMed  Google Scholar 

  • Cuervo AM, Wong E (2014) Chaperone-mediated autophagy: roles in disease and aging. Cell Res 24(1):92–104

    Article  CAS  PubMed  Google Scholar 

  • Cuervo AM, Knecht E, Terlecky SR, Dice JF (1995) Activation of a selective pathway of lysosomal proteolysis in rat liver by prolonged starvation. Am J Phys 269(5 Pt 1):C1200–C1208

    Article  CAS  Google Scholar 

  • Dengjel J, Schoor O, Fischer R, Reich M, Kraus M, Muller M, Kreymborg K, Altenberend F, Brandenburg J, Kalbacher H et al (2005) Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc Natl Acad Sci U S A 102(22):7922–7927

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Deretic V, Saitoh T, Akira S (2013) Autophagy in infection, inflammation and immunity. Nat Rev Immunol 13(10):722–737

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • English L, Chemali M, Duron J, Rondeau C, Laplante A, Gingras D, Alexander D, Leib D, Norbury C, Lippe R et al (2009) Autophagy enhances the presentation of endogenous viral antigens on MHC class I molecules during HSV-1 infection. Nat Immunol 10(5):480–487

    Article  CAS  PubMed  Google Scholar 

  • Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 69(Suppl 1):S4–S9

    Article  PubMed  Google Scholar 

  • Fulop T, Larbi A, Pawelec G (2013) Human T cell aging and the impact of persistent viral infections. Front Immunol 4:271

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fulop T, Le Page A, Fortin C, Witkowski JM, Dupuis G, Larbi A (2014) Cellular signaling in the aging immune system. Curr Opin Immunol 29:105–111

    Article  CAS  PubMed  Google Scholar 

  • Fulop T, McElhaney J, Pawelec G, Cohen AA, Morais JA, Dupuis G, Baehl S, Camous X, Witkowski JM, Larbi A (2015) Frailty, inflammation and immunosenescence. Interdiscip Top Gerontol Geriatr 41:26–40

    PubMed  Google Scholar 

  • Garcia-Prat L, Martinez-Vicente M, Perdiguero E, Ortet L, Rodriguez-Ubreva J, Rebollo E, Ruiz-Bonilla V, Gutarra S, Ballestar E, Serrano AL et al (2016) Autophagy maintains stemness by preventing senescence. Nature 529(7584):37–42

    Article  CAS  PubMed  Google Scholar 

  • Goronzy JJ, Weyand CM (2013) Understanding immunosenescence to improve responses to vaccines. Nat Immunol 14(5):428–436

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Goronzy JJ, Lee WW, Weyand CM (2007) Aging and T-cell diversity. Exp Gerontol 42(5):400–406

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Goronzy JJ, Li G, Yu M, Weyand CM (2012) Signaling pathways in aged T cells – a reflection of T cell differentiation, cell senescence and host environment. Semin Immunol 24(5):365–372

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hailey DW, Rambold AS, Satpute-Krishnan P, Mitra K, Sougrat R, Kim PK, Lippincott-Schwartz J (2010) Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 141(4):656–667

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Haq K, McElhaney JE (2014) Immunosenescence: influenza vaccination and the elderly. Curr Opin Immunol 29:38–42

    Article  CAS  PubMed  Google Scholar 

  • Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H et al (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441(7095):885–889

    Article  CAS  PubMed  Google Scholar 

  • Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS et al (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460(7253):392–395

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hayashi-Nishino M, Fujita N, Noda T, Yamaguchi A, Yoshimori T, Yamamoto A (2009) A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Nat Cell Biol 11(12):1433–1437

    Article  CAS  PubMed  Google Scholar 

  • Henson SM, Lanna A, Riddell NE, Franzese O, Macaulay R, Griffiths SJ, Puleston DJ, Watson AS, Simon AK, Tooze SA et al (2014) p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8(+) T cells. J Clin Invest 124(9):4004–4016

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Herndler-Brandstetter D, Ishigame H, Flavell RA (2013) How to define biomarkers of human T cell aging and immunocompetence? Front Immunol 4:136

    PubMed Central  PubMed  Google Scholar 

  • Hewitt G, Korolchuk VI (2017) Repair, reuse, recycle: the expanding role of autophagy in genome maintenance. Trends Cell Biol 27(5):340–351

    Article  CAS  PubMed  Google Scholar 

  • Hubbard VM, Valdor R, Patel B, Singh R, Cuervo AM, Macian F (2010) Macroautophagy regulates energy metabolism during effector T cell activation. J Immunol 185(12):7349–7357

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hubbard VM, Valdor R, Macian F, Cuervo AM (2012) Selective autophagy in the maintenance of cellular homeostasis in aging organisms. Biogerontology 13(1):21–35

    Article  PubMed  Google Scholar 

  • Itakura E, Kishi C, Inoue K, Mizushima N (2008) Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol Biol Cell 19(12):5360–5372

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jagannath C, Lindsey DR, Dhandayuthapani S, Xu Y, Hunter RL Jr, Eissa NT (2009) Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells. Nat Med 15(3):267–276

    Article  CAS  PubMed  Google Scholar 

  • Jia W, Pua HH, Li QJ, He YW (2011) Autophagy regulates endoplasmic reticulum homeostasis and calcium mobilization in T lymphocytes. J Immunol 186(3):1564–1574

    Article  CAS  PubMed  Google Scholar 

  • Jia W, He MX, McLeod IX, Guo J, Ji D, He YW (2015) Autophagy regulates T lymphocyte proliferation through selective degradation of the cell-cycle inhibitor CDKN1B/p27Kip1. Autophagy 11(12):2335–2345

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kabat AM, Harrison OJ, Riffelmacher T, Moghaddam AE, Pearson CF, Laing A, Abeler-Dorner L, Forman SP, Grencis RK, Sattentau Q et al (2016) The autophagy gene Atg16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation. elife 5:e12444

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19(21):5720–5728

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kaushik S, Cuervo AM (2018) The coming of age of chaperone-mediated autophagy. Nat Rev Mol Cell Biol 19(6):365–381

    Article  CAS  PubMed  Google Scholar 

  • Kaushik S, Massey AC, Cuervo AM (2006) Lysosome membrane lipid microdomains: novel regulators of chaperone-mediated autophagy. EMBO J 25(17):3921–3933

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kaushik S, Singh R, Cuervo AM (2010) Autophagic pathways and metabolic stress. Diabetes Obes Metab 12(Suppl 2):4–14

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kaushik S, Rodriguez-Navarro JA, Arias E, Kiffin R, Sahu S, Schwartz GJ, Cuervo AM, Singh R (2011) Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance. Cell Metab 14(2):173–183

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kennedy BK, Berger SL, Brunet A, Campisi J, Cuervo AM, Epel ES, Franceschi C, Lithgow GJ, Morimoto RI, Pessin JE et al (2014) Geroscience: linking aging to chronic disease. Cell 159(4):709–713

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kiffin R, Christian C, Knecht E, Cuervo AM (2004) Activation of chaperone-mediated autophagy during oxidative stress. Mol Biol Cell 15(11):4829–4840

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kiffin R, Kaushik S, Zeng M, Bandyopadhyay U, Zhang C, Massey AC, Martinez-Vicente M, Cuervo AM (2007) Altered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age. J Cell Sci 120(Pt 5):782–791

    Article  CAS  PubMed  Google Scholar 

  • Koga H, Kaushik S, Cuervo AM (2010) Altered lipid content inhibits autophagic vesicular fusion. FASEB J 24(8):3052–3065

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kroemer G (2015) Autophagy: a druggable process that is deregulated in aging and human disease. J Clin Invest 125(1):1–4

    Article  PubMed Central  PubMed  Google Scholar 

  • Kroemer G, Marino G, Levine B (2010) Autophagy and the integrated stress response. Mol Cell 40(2):280–293

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lages CS, Lewkowich I, Sproles A, Wills-Karp M, Chougnet C (2010) Partial restoration of T-cell function in aged mice by in vitro blockade of the PD-1/ PD-L1 pathway. Aging Cell 9(5):785–798

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Levine B, Deretic V (2007) Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol 7(10):767–777

    Article  CAS  PubMed  Google Scholar 

  • Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402(6762):672–676

    Article  CAS  PubMed  Google Scholar 

  • Lipinski MM, Zheng B, Lu T, Yan Z, Py BF, Ng A, Xavier RJ, Li C, Yankner BA, Scherzer CR et al (2010) Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer’s disease. Proc Natl Acad Sci U S A 107(32):14164–14169

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Loi M, Muller A, Steinbach K, Niven J, Barreira da Silva R, Paul P, Ligeon LA, Caruso A, Albrecht RA, Becker AC et al (2016) Macroautophagy proteins control MHC class I levels on dendritic cells and shape anti-viral CD8(+) T cell responses. Cell Rep 15(5):1076–1087

    Article  CAS  PubMed  Google Scholar 

  • Macri C, Wang F, Tasset I, Schall N, Page N, Briand JP, Cuervo AM, Muller S (2015) Modulation of deregulated chaperone-mediated autophagy by a phosphopeptide. Autophagy 11(3):472–486

    Article  PubMed Central  PubMed  Google Scholar 

  • Martinez-Martin N, Maldonado P, Gasparrini F, Frederico B, Aggarwal S, Gaya M, Tsui C, Burbage M, Keppler SJ, Montaner B et al (2017) A switch from canonical to noncanonical autophagy shapes B cell responses. Science 355(6325):641–647

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Maue AC, Haynes L (2009) CD4+ T cells and immunosenescence – a mini-review. Gerontology 55(5):491–495

    Article  PubMed  Google Scholar 

  • Melendez A, Talloczy Z, Seaman M, Eskelinen EL, Hall DH, Levine B (2003) Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301(5638):1387–1391

    Article  CAS  PubMed  Google Scholar 

  • Miller BC, Zhao Z, Stephenson LM, Cadwell K, Pua HH, Lee HK, Mizushima NN, Iwasaki A, He YW, Swat W et al (2008) The autophagy gene ATG5 plays an essential role in B lymphocyte development. Autophagy 4(3):309–314

    Article  CAS  PubMed  Google Scholar 

  • Mizushima N (2011) Autophagy in protein and organelle turnover. Cold Spring Harb Symp Quant Biol 76:397–402

    Article  CAS  PubMed  Google Scholar 

  • Mizushima N, Noda T, Yoshimori T, Tanaka Y, Ishii T, George MD, Klionsky DJ, Ohsumi M, Ohsumi Y (1998) A protein conjugation system essential for autophagy. Nature 395(6700):395–398

    Article  CAS  PubMed  Google Scholar 

  • Mizushima N, Yoshimori T, Ohsumi Y (2011) The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol 27:107–132

    Article  CAS  PubMed  Google Scholar 

  • Mocholi E, Dowling SD, Botbol Y, Gruber RC, Ray AK, Vastert S, Shafit-Zagardo B, Coffer PJ, Macian F (2018) Autophagy is a tolerance-avoidance mechanism that modulates TCR-mediated signaling and cell metabolism to prevent induction of T cell anergy. Cell Rep 24(5):1136–1150

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Morimoto RI, Cuervo AM (2014) Proteostasis and the aging proteome in health and disease. J Gerontol A Biol Sci Med Sci 69(Suppl 1):S33–S38

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Morozova K, Clement CC, Kaushik S, Stiller B, Arias E, Ahmad A, Rauch JN, Chatterjee V, Melis C, Scharf B et al (2016) Structural and biological interaction of hsc-70 protein with phosphatidylserine in endosomal microautophagy. J Biol Chem 291(35):18096–18106

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mortensen M, Soilleux EJ, Djordjevic G, Tripp R, Lutteropp M, Sadighi-Akha E, Stranks AJ, Glanville J, Knight S, Jacobsen SE et al (2011) The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. J Exp Med 208(3):455–467

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Munz C (2016) Autophagy proteins in antigen processing for presentation on MHC molecules. Immunol Rev 272(1):17–27

    Article  CAS  PubMed  Google Scholar 

  • Nedjic J, Aichinger M, Emmerich J, Mizushima N, Klein L (2008) Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance. Nature 455(7211):396–400

    Article  CAS  PubMed  Google Scholar 

  • Panda A, Arjona A, Sapey E, Bai F, Fikrig E, Montgomery RR, Lord JM, Shaw AC (2009) Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol 30(7):325–333

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Park C, Suh Y, Cuervo AM (2015) Regulated degradation of Chk1 by chaperone-mediated autophagy in response to DNA damage. Nat Commun 6:6823

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Paul S, Kashyap AK, Jia W, He YW, Schaefer BC (2012) Selective autophagy of the adaptor protein Bcl10 modulates T cell receptor activation of NF-kappaB. Immunity 36(6):947–958

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pawelec G (2014) Immunosenenescence: role of cytomegalovirus. Exp Gerontol 54:1–5

    Article  CAS  PubMed  Google Scholar 

  • Pengo N, Scolari M, Oliva L, Milan E, Mainoldi F, Raimondi A, Fagioli C, Merlini A, Mariani E, Pasqualetto E et al (2013) Plasma cells require autophagy for sustainable immunoglobulin production. Nat Immunol 14(3):298–305

    Article  CAS  PubMed  Google Scholar 

  • Phadwal K, Alegre-Abarrategui J, Watson AS, Pike L, Anbalagan S, Hammond EM, Wade-Martins R, McMichael A, Klenerman P, Simon AK (2012) A novel method for autophagy detection in primary cells: impaired levels of macroautophagy in immunosenescent T cells. Autophagy 8(4):677–689

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pickles S, Vigie P, Youle RJ (2018) Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr Biol 28(4):R170–r185

    Article  CAS  PubMed  Google Scholar 

  • Pua HH, Dzhagalov I, Chuck M, Mizushima N, He YW (2007) A critical role for the autophagy gene Atg5 in T cell survival and proliferation. J Exp Med 204(1):25–31

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pua HH, Guo J, Komatsu M, He YW (2009) Autophagy is essential for mitochondrial clearance in mature T lymphocytes. J Immunol 182(7):4046–4055

    Article  CAS  PubMed  Google Scholar 

  • Puleston DJ, Zhang H, Powell TJ, Lipina E, Sims S, Panse I, Watson AS, Cerundolo V, Townsend AR, Klenerman P et al (2014) Autophagy is a critical regulator of memory CD8(+) T cell formation. elife 3:03706

    Article  Google Scholar 

  • Pyo JO, Yoo SM, Ahn HH, Nah J, Hong SH, Kam TI, Jung S, Jung YK (2013) Overexpression of Atg5 in mice activates autophagy and extends lifespan. Nat Commun 4:2300

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ravikumar B, Moreau K, Jahreiss L, Puri C, Rubinsztein DC (2010) Plasma membrane contributes to the formation of pre-autophagosomal structures. Nat Cell Biol 12(8):747–757

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Raz Y, Guerrero-Ros I, Maier A, Slagboom PE, Atzmon G, Barzilai N, Macian F (2017) Activation-induced autophagy is preserved in CD4+ T-cells in familial longevity. J Gerontol A Biol Sci Med Sci 72(9):1201–1206

    Article  PubMed Central  PubMed  Google Scholar 

  • Reynolds LM, Ding J, Taylor JR, Lohman K, Soranzo N, de la Fuente A, Liu TF, Johnson C, Barr RG, Register TC et al (2015) Transcriptomic profiles of aging in purified human immune cells. BMC Genomics 16:333

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rivera Vargas T, Cai Z, Shen Y, Dosset M, Benoit-Lizon I, Martin T, Roussey A, Flavell RA, Ghiringhelli F, Apetoh L (2017) Selective degradation of PU.1 during autophagy represses the differentiation and antitumour activity of TH9 cells. Nat Commun 8(1):559

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rubinsztein DC, Marino G, Kroemer G (2011) Autophagy and aging. Cell 146(5):682–695

    Article  CAS  PubMed  Google Scholar 

  • Sahu R, Kaushik S, Clement CC, Cannizzo ES, Scharf B, Follenzi A, Potolicchio I, Nieves E, Cuervo AM, Santambrogio L (2011) Microautophagy of cytosolic proteins by late endosomes. Dev Cell 20(1):131–139

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sanderson SL, Simon AK (2017) In aged primary T cells, mitochondrial stress contributes to telomere attrition measured by a novel imaging flow cytometry assay. Aging Cell 16(6):1234–1243

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Santambrogio L, Cuervo AM (2011) Chasing the elusive mammalian microautophagy. Autophagy 7(6):652–654

    Article  PubMed  Google Scholar 

  • Schmid D, Pypaert M, Munz C (2007) Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity 26(1):79–92

    Article  CAS  PubMed  Google Scholar 

  • Schneider JL, Cuervo AM (2014) Autophagy and human disease: emerging themes. Curr Opin Genet Dev 26:16–23

    Article  CAS  PubMed  Google Scholar 

  • Schneider JL, Suh Y, Cuervo AM (2014) Deficient chaperone-mediated autophagy in liver leads to metabolic dysregulation. Cell Metab 20(3):417–432

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Shimatani K, Nakashima Y, Hattori M, Hamazaki Y, Minato N (2009) PD-1+ memory phenotype CD4+ T cells expressing C/EBPalpha underlie T cell immunodepression in senescence and leukemia. Proc Natl Acad Sci U S A 106(37):15807–15812

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Singh R, Cuervo AM (2011) Autophagy in the cellular energetic balance. Cell Metab 13(5):495–504

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Singh R, Kaushik S, Wang Y, Xiang Y, Novak I, Komatsu M, Tanaka K, Cuervo AM, Czaja MJ (2009) Autophagy regulates lipid metabolism. Nature 458(7242):1131–1135

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stanley RE, Ragusa MJ, Hurley JH (2014) The beginning of the end: how scaffolds nucleate autophagosome biogenesis. Trends Cell Biol 24(1):73–81

    Article  CAS  PubMed  Google Scholar 

  • Stolz A, Ernst A, Dikic I (2014) Cargo recognition and trafficking in selective autophagy. Nat Cell Biol 16(6):495–501

    Article  CAS  PubMed  Google Scholar 

  • Valdor R, Macian F (2012) Autophagy and the regulation of the immune response. Pharmacol Res 66(6):475–483

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Valdor R, Mocholi E, Botbol Y, Guerrero-Ros I, Chandra D, Koga H, Gravekamp C, Cuervo AM, Macian F (2014) Chaperone-mediated autophagy regulates T cell responses through targeted degradation of negative regulators of T cell activation. Nat Immunol 15(11):1046–1054

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wang Y, Li L, Hou C, Lai Y, Long J, Liu J, Zhong Q, Diao J (2016) SNARE-mediated membrane fusion in autophagy. Semin Cell Dev Biol 60:97–104

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wei J, Long L, Yang K, Guy C, Shrestha S, Chen Z, Wu C, Vogel P, Neale G, Green DR et al (2016) Autophagy enforces functional integrity of regulatory T cells by coupling environmental cues and metabolic homeostasis. Nat Immunol 17(3):277–285

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Weng NP, Levine BL, June CH, Hodes RJ (1996) Regulated expression of telomerase activity in human T lymphocyte development and activation. J Exp Med 183(6):2471–2479

    Article  CAS  PubMed  Google Scholar 

  • Whang MI, Tavares RM, Benjamin DI, Kattah MG, Advincula R, Nomura DK, Debnath J, Malynn BA, Ma A (2017) The ubiquitin binding protein TAX1BP1 mediates autophagosome induction and the metabolic transition of activated T cells. Immunity 46(3):405–420

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Willinger T, Flavell RA (2012) Canonical autophagy dependent on the class III phosphoinositide-3 kinase Vps34 is required for naive T-cell homeostasis. Proc Natl Acad Sci U S A 109(22):8670–8675

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Xu X, Araki K, Li S, Han JH, Ye L, Tan WG, Konieczny BT, Bruinsma MW, Martinez J, Pearce EL et al (2014) Autophagy is essential for effector CD8(+) T cell survival and memory formation. Nat Immunol 15(12):1152–1161

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zaffagnini G, Martens S (2016) Mechanisms of selective autophagy. J Mol Biol 428(9 Pt A):1714–1724

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang C, Cuervo AM (2008) Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nat Med 14(9):959–965

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang H, Puleston DJ, Simon AK (2016) Autophagy and immune senescence. Trends Mol Med 22(8):671–686

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fernando Macian .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Macian, F. (2019). Autophagy and T Cell Aging. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook of Immunosenescence. Springer, Cham. https://doi.org/10.1007/978-3-319-64597-1_112-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-64597-1_112-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-64597-1

  • Online ISBN: 978-3-319-64597-1

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics