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Autophagy in Infection and Immunity pp 85–105Cite as

Autophagy and Lymphocyte Homeostasis

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 335))

Abstract

Lymphocyte homeostasis is tightly regulated in vivo by various factors including cytokines, antigens, and costimulatory signals. Central to this regulation is the intricate balance between survival and apoptosis determined by pro- and antiapoptotic factors, including Bcl-2/Bcl-xL of the Bcl-2 family in the intrinsic death pathway and Fas/FADD of the TNF death receptor superfamily in the extrinsic death pathway. Recent studies have identified a critical role for autophagy, a well-conserved catabolic process in eukaryotic cells, in T and B lymphocyte homeostasis. Autophagy is essential for mature T lymphocyte survival and proliferation. In addition, autophagy can promote T cell death in defined physiologic or pathologic conditions. Autophagy also contributes to the survival of subsets of B lymphocytes, including developing pre-B cells as well as B1 B cells in vivo. Thus, autophagy represents a novel pathway regulating both developing and mature lymphocytes. Future studies are required to investigate the role of autophagy in regulating T and B cell homeostasis during immune responses to pathogens, as well as to define the mechanisms by which autophagy regulates lymphocyte death and survival.

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References

  • Agenes F, Freitas AA (1999) Transfer of small resting B cells into immunodeficient hosts results in the selection of a self-renewing activated B cell population. J Exp Med 189:319–330

    Article  CAS  PubMed  Google Scholar 

  • Amaravadi RK, Yu D, Lum JJ, Bui T, Christophorou MA, Evan GI, Thomas-Tikhonenko A, Thompson CB (2007) Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest 117:326–336

    Article  CAS  PubMed  Google Scholar 

  • Arsov I, Li X, Matthews G, Coradin J, Hartmann B, Simon AK, Sealfon SC, Yue Z (2008) BAC-mediated transgenic expression of fluorescent autophagic protein Beclin 1 reveals a role for Beclin 1 in lymphocyte development. Cell Death Differ 15:1385–1395

    Article  CAS  PubMed  Google Scholar 

  • Baba M, Takeshige K, Baba N, Ohsumi Y (1994) Ultrastructural analysis of the autophagic process in yeast: detection of autophagosomes and their characterization. J Cell Biol 124:903–913

    Article  CAS  PubMed  Google Scholar 

  • Badovinac VP, Harty JT (2006) Programming, demarcating, and manipulating CD8+ T-cell memory. Immunol Rev 211:67–80

    Article  CAS  PubMed  Google Scholar 

  • Baehrecke EH (2005) Autophagy: dual roles in life and death? Nat Rev Mol Cell Biol 6:505–510

    Article  CAS  PubMed  Google Scholar 

  • Bassnett S (2002) Lens organelle degradation. Exp Eye Res 74:1–6

    Article  CAS  PubMed  Google Scholar 

  • Becker TC, Wherry EJ, Boone D, Murali-Krishna K, Antia R, Ma A, Ahmed R (2002) Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells. J Exp Med 195:1541–1548

    Article  CAS  PubMed  Google Scholar 

  • Beisner DR, Chu IH, Arechiga AF, Hedrick SM, Walsh CM (2003) The requirements for Fas-associated death domain signaling in mature T cell activation and survival. J Immunol 171:247–256

    CAS  PubMed  Google Scholar 

  • Bender J, Mitchell T, Kappler J, Marrack P (1999) CD4+ T cell division in irradiated mice requires peptides distinct from those responsible for thymic selection. J Exp Med 190:367–374

    Article  CAS  PubMed  Google Scholar 

  • Berry DL, Baehrecke EH (2007) Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila. Cell 131:1137–1148

    Article  CAS  PubMed  Google Scholar 

  • Beutner U, MacDonald HR (1998) TCR-MHC class II interaction is required for peripheral expansion of CD4 cells in a T cell-deficient host. Int Immunol 10:305–310

    Article  CAS  PubMed  Google Scholar 

  • Blattman JN, Antia R, Sourdive DJ, Wang X, Kaech SM, Murali-Krishna K, Altman JD, Ahmed R (2002) Estimating the precursor frequency of naive antigen-specific CD8 T cells. J Exp Med 195:657–664

    Article  CAS  PubMed  Google Scholar 

  • Boise LH, Minn AJ, June CH, Lindsten T, Thompson CB (1995) Growth factors can enhance lymphocyte survival without committing the cell to undergo cell division. Proc Natl Acad Sci USA 92:5491–5495

    Article  CAS  PubMed  Google Scholar 

  • Bouillet P, Purton JF, Godfrey DI, Zhang LC, Coultas L, Puthalakath H, Pellegrini M, Cory S, Adams JM, Strasser A (2002) BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes. Nature 415:922–926

    Article  CAS  PubMed  Google Scholar 

  • Brocker T (1997) Survival of mature CD4 T lymphocytes is dependent on major histocompatibility complex class II-expressing dendritic cells. J Exp Med 186:1223–1232

    Article  CAS  PubMed  Google Scholar 

  • Broome HE, Dargan CM, Krajewski S, Reed JC (1995) Expression of Bcl-2, Bcl-x, and Bax after T cell activation and IL-2 withdrawal. J Immunol 155:2311–2317

    CAS  PubMed  Google Scholar 

  • Cabatingan MS, Schmidt MR, Sen R, Woodland RT (2002) Naive B lymphocytes undergo homeostatic proliferation in response to B cell deficit. J Immunol 169:6795–6805

    CAS  PubMed  Google Scholar 

  • Codogno P, Meijer AJ (2005) Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ 12(Suppl 2):1509–1518

    Article  CAS  PubMed  Google Scholar 

  • Colell A, Ricci JE, Tait S, Milasta S, Maurer U, Bouchier-Hayes L, Fitzgerald P, Guio-Carrion A, Waterhouse NJ, Li CW et al (2007) GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation. Cell 129:983–997

    Article  CAS  PubMed  Google Scholar 

  • Corazza N, Brumatti G, Jakob S, Villunger A, Brunner T (2004) TRAIL and thymocyte apoptosis: not so deadly? Cell Death Differ 11(Suppl 2):S213–S215

    Article  CAS  PubMed  Google Scholar 

  • Cretney E, Uldrich AP, Berzins SP, Strasser A, Godfrey DI, Smyth MJ (2003) Normal thymocyte negative selection in TRAIL-deficient mice. J Exp Med 198:491–496

    Article  CAS  PubMed  Google Scholar 

  • Crowley JE, Scholz JL, Quinn Iii WJ, Stadanlick JE, Treml JF, Treml LS, Hao Y, Goenka R, O’Neill PJ, Matthews AHet al (2008) Homeostatic control of B lymphocyte subsets. Immunol Res 42:75–83

    Article  PubMed  Google Scholar 

  • Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116:205–219

    Article  CAS  PubMed  Google Scholar 

  • Diehl GE, Yue HH, Hsieh K, Kuang AA, Ho M, Morici LA, Lenz LL, Cado D, Riley LW, Winoto A (2004) TRAIL-R as a negative regulator of innate immune cell responses. Immunity 21:877–889

    Article  CAS  PubMed  Google Scholar 

  • Dorfman JR, Germain RN (2002) MHC-dependent survival of naive T cells? A complicated answer to a simple question. Microbes Infect 4:547–554

    Article  CAS  PubMed  Google Scholar 

  • Dzhagalov I, Dunkle A, He YW (2008) The anti-apoptotic Bcl-2 family member Mcl-1 promotes T lymphocyte survival at multiple stages. J Immunol 181:521–528

    CAS  PubMed  Google Scholar 

  • El Kassar N, Lucas PJ, Klug DB, Zamisch M, Merchant M, Bare CV, Choudhury B, Sharrow SO, Richie E, Mackall CL et al (2004) A dose effect of IL-7 on thymocyte development. Blood 104:1419–1427

    Article  CAS  PubMed  Google Scholar 

  • Elmore SP, Qian T, Grissom SF, Lemasters JJ (2001) The mitochondrial permeability transition initiates autophagy in rat hepatocytes. Faseb J 15:2286–2287

    CAS  PubMed  Google Scholar 

  • Erickson SL, de Sauvage FJ, Kikly K, Carver-Moore K, Pitts-Meek S, Gillett N, Sheehan KC, Schreiber RD, Goeddel DV, Moore MW (1994) Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice. Nature 372:560–563

    Article  CAS  PubMed  Google Scholar 

  • Ernst B, Lee DS, Chang JM, Sprent J, Surh CD (1999) The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery. Immunity 11:173–181

    Article  CAS  PubMed  Google Scholar 

  • Espert L, Denizot M, Grimaldi M, Robert-Hebmann V, Gay B, Varbanov M, Codogno P, Biard-Piechaczyk M (2006) Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4. J Clin Invest 116:2161–2172

    Article  CAS  PubMed  Google Scholar 

  • Fehniger TA, Suzuki K, Ponnappan A, VanDeusen JB, Cooper MA, Florea SM, Freud AG, Robinson ML, Durbin J, Caligiuri MA (2001) Fatal leukemia in interleukin 15 transgenic mice follows early expansions in natural killer and memory phenotype CD8+ T cells. J Exp Med 193:219–231

    Article  CAS  PubMed  Google Scholar 

  • Gerland LM, Genestier L, Peyrol S, Michallet MC, Hayette S, Urbanowicz I, Ffrench P, Magaud JP, Ffrench M (2004) Autolysosomes accumulate during in vitro CD8+ T-lymphocyte aging and may participate in induced death sensitization of senescent cells. Exp Gerontol 39:789–800

    Article  CAS  Google Scholar 

  • Goldrath AW, Bevan MJ (1999a) Low-affinity ligands for the TCR drive proliferation of mature CD8+ T cells in lymphopenic hosts. Immunity 11:183–190

    Article  CAS  PubMed  Google Scholar 

  • Goldrath AW, Bevan MJ (1999b) Selecting and maintaining a diverse T-cell repertoire. Nature 402:255–262

    Article  CAS  PubMed  Google Scholar 

  • Goldrath AW, Sivakumar PV, Glaccum M, Kennedy MK, Bevan MJ, Benoist C, Mathis D, Butz EA (2002) Cytokine requirements for acute and basal homeostatic proliferation of naive and memory CD8+ T cells. J Exp Med 195:1515–1522

    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 Het al (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441:885–889

    Article  CAS  PubMed  Google Scholar 

  • He YW, Malek TR (1998) The structure and function of gamma c-dependent cytokines and receptors: regulation of T lymphocyte development and homeostasis. Crit Rev Immunol 18:503–524

    CAS  PubMed  Google Scholar 

  • Hildeman DA, Zhu Y, Mitchell TC, Bouillet P, Strasser A, Kappler J, Marrack P (2002) Activated T cell death in vivo mediated by proapoptotic bcl-2 family member bim. Immunity 16:759–767

    Article  CAS  PubMed  Google Scholar 

  • Hoyer-Hansen M, Bastholm L, Szyniarowski P, Campanella M, Szabadkai G, Farkas T, Bianchi K, Fehrenbacher N, Elling F, Rizzuto Ret al (2007) Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-beta, and Bcl-2. Mol Cell 25:193–205

    Article  PubMed  CAS  Google Scholar 

  • Hughes PD, Belz GT, Fortner KA, Budd RC, Strasser A, Bouillet P (2008) Apoptosis regulators Fas and Bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity. Immunity 28:197–205

    Article  CAS  PubMed  Google Scholar 

  • Jameson SC (2002) Maintaining the norm: T-cell homeostasis. Nat Rev Immunol 2:547–556

    CAS  PubMed  Google Scholar 

  • Janssen EM, Droin NM, Lemmens EE, Pinkoski MJ, Bensinger SJ, Ehst BD, Griffith TS, Green DR, Schoenberger SP (2005) CD4+ T-cell help controls CD8+ T-cell memory via TRAIL-mediated activation-induced cell death. Nature 434:88–93

    Article  CAS  PubMed  Google Scholar 

  • Jia L, Dourmashkin RR, Allen PD, Gray AB, Newland AC, Kelsey SM (1997) Inhibition of autophagy abrogates tumour necrosis factor alpha induced apoptosis in human T-lymphoblastic leukaemic cells. Br J Haematol 98:673–685

    Article  CAS  PubMed  Google Scholar 

  • Judge AD, Zhang X, Fujii H, Surh CD, Sprent J (2002) Interleukin 15 controls both proliferation and survival of a subset of memory-phenotype CD8(+) T cells. J Exp Med 196:935–946

    Article  CAS  PubMed  Google Scholar 

  • Kassiotis G, Garcia S, Simpson E, Stockinger B (2002) Impairment of immunological memory in the absence of MHC despite survival of memory T cells. Nat Immunol 3:244–250

    Article  CAS  PubMed  Google Scholar 

  • Kennedy MK, Glaccum M, Brown SN, Butz EA, Viney JL, Embers M, Matsuki N, Charrier K, Sedger L, Willis CRet al (2000) Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med 191:771–780

    Article  CAS  PubMed  Google Scholar 

  • Kent G, Minick OT, Volini FI, Orfei E (1966) Autophagic vacuoles in human red cells. Am J Pathol 48:831–857

    CAS  PubMed  Google Scholar 

  • Kieper WC, Tan JT, Bondi-Boyd B, Gapin L, Sprent J, Ceredig R, Surh CD (2002) Overexpression of interleukin (IL)-7 leads to IL-15-independent generation of memory phenotype CD8+ T cells. J Exp Med 195:1533–1539

    Article  CAS  PubMed  Google Scholar 

  • Kirberg J, Berns A, von Boehmer H (1997) Peripheral T cell survival requires continual ligation of the T cell receptor to major histocompatibility complex-encoded molecules. J Exp Med 186:1269–1275

    Article  CAS  PubMed  Google Scholar 

  • Kishimoto H, Surh CD, Sprent J (1998) A role for Fas in negative selection of thymocytes in vivo. J Exp Med 187:1427–1438

    Article  CAS  PubMed  Google Scholar 

  • Kissova I, Salin B, Schaeffer J, Bhatia S, Manon S, Camougrand N (2007) Selective and non-selective autophagic degradation of mitochondria in yeast. Autophagy 3:329–336

    CAS  PubMed  Google Scholar 

  • Klionsky DJ, Emr SD (2000) Autophagy as a regulated pathway of cellular degradation. Science 290:1717–1721

    Article  CAS  PubMed  Google Scholar 

  • Knudson CM, Korsmeyer SJ (1997) Bcl-2 and Bax function independently to regulate cell death. Nat Genet 16:358–363

    Article  CAS  PubMed  Google Scholar 

  • Knudson CM, Tung KS, Tourtellotte WG, Brown GA, Korsmeyer SJ (1995) Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science 270:96–99

    Article  CAS  PubMed  Google Scholar 

  • Komatsu M, Waguri S, Ueno T, Iwata J, Murata S, Tanida I, Ezaki J, Mizushima N, Ohsumi Y, Uchiyama Y et al (2005) Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol 169:425–434

    Article  CAS  PubMed  Google Scholar 

  • Komatsu M, Waguri S, Chiba T, Murata S, Iwata J, Tanida I, Ueno T, Koike M, Uchiyama Y, Kominami E et al (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441:880–884

    Article  CAS  PubMed  Google Scholar 

  • Kondrack RM, Harbertson J, Tan JT, McBreen ME, Surh CD, Bradley LM (2003) Interleukin 7 regulates the survival and generation of memory CD4 cells. J Exp Med 198:1797–1806

    Article  CAS  PubMed  Google Scholar 

  • Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, Yoshimori T, Ohsumi Y, Tokuhisa T, Mizushima N (2004) The role of autophagy during the early neonatal starvation period. Nature 432:1032–1036

    Article  CAS  PubMed  Google Scholar 

  • Lamhamedi-Cherradi SE, Zheng SJ, Maguschak KA, Peschon J, Chen YH (2003) Defective thymocyte apoptosis and accelerated autoimmune diseases in TRAIL–/– mice. Nat Immunol 4:255–260

    Article  CAS  PubMed  Google Scholar 

  • Lau LL, Jamieson BD, Somasundaram T, Ahmed R (1994) Cytotoxic T-cell memory without antigen. Nature 369:648–652

    Article  CAS  PubMed  Google Scholar 

  • Lenz DC, Kurz SK, Lemmens E, Schoenberger SP, Sprent J, Oldstone MB, Homann D (2004) IL-7 regulates basal homeostatic proliferation of antiviral CD4+ T cell memory. Proc Natl Acad Sci USA 101:9357–9362

    Article  CAS  PubMed  Google Scholar 

  • Levine B, Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 132:27–42

    Article  CAS  PubMed  Google Scholar 

  • Li C, Capan E, Zhao Y, Zhao J, Stolz D, Watkins SC, Jin S, Lu B (2006) Autophagy is induced in CD4+ T cells and important for the growth factor-withdrawal cell death. J Immunol 177:5163–5168

    CAS  PubMed  Google Scholar 

  • Liang J, Shao SH, Xu ZX, Hennessy B, Ding Z, Larrea M, Kondo S, Dumont DJ, Gutterman JU, Walker CLet al (2007) The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nat Cell Biol 9:218–224

    Article  CAS  PubMed  Google Scholar 

  • Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G, Herman B, Levine B (1998) Protection against fatal Sindbis virus encephalitis by Beclin, a novel Bcl-2-interacting protein. J Virol 72:8586–8596

    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 402:672–676

    Article  CAS  PubMed  Google Scholar 

  • Lindsten T, Ross AJ, King A, Zong WX, Rathmell JC, Shiels HA, Ulrich E, Waymire KG, Mahar P, Frauwirth Ket al (2000) The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol Cell 6:1389–1399

    Article  CAS  PubMed  Google Scholar 

  • Linette GP, Li Y, Roth K, Korsmeyer SJ (1996) Cross talk between cell death and cell cycle progression: BCL-2 regulates NFAT-mediated activation. Proc Natl Acad Sci USA 93:9545–9552

    Article  CAS  PubMed  Google Scholar 

  • Lodolce JP, Boone DL, Chai S, Swain RE, Dassopoulos T, Trettin S, Ma A (1998) IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity 9:669–676

    Article  CAS  PubMed  Google Scholar 

  • Lum JJ, Bauer DE, Kong M, Harris MH, Li C, Lindsten T, Thompson CB (2005) Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 120:237–248

    Article  CAS  PubMed  Google Scholar 

  • Maraskovsky E, O’Reilly LA, Teepe M, Corcoran LM, Peschon JJ, Strasser A (1997) Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1–/– mice. Cell 89:1011–1019

    Article  CAS  PubMed  Google Scholar 

  • Marks-Konczalik J, Dubois S, Losi JM, Sabzevari H, Yamada N, Feigenbaum L, Waldmann TA, Tagaya Y (2000) IL-2-induced activation-induced cell death is inhibited in IL-15 transgenic mice. Proc Natl Acad Sci USA 97:11445–11450

    Article  CAS  PubMed  Google Scholar 

  • Marrack P, Bender J, Hildeman D, Jordan M, Mitchell T, Murakami M, Sakamoto A, Schaefer BC, Swanson B, Kappler J (2000) Homeostasis of alpha beta TCR+ T cells. Nat Immunol 1:107–111

    Article  CAS  PubMed  Google Scholar 

  • Matsui M, Yamamoto A, Kuma A, Ohsumi Y, Mizushima N (2006) Organelle degradation during the lens and erythroid differentiation is independent of autophagy. Biochem Biophys Res Commun 339:485–489

    Article  CAS  PubMed  Google Scholar 

  • Matsui Y, Takagi H, Qu X, Abdellatif M, Sakoda H, Asano T, Levine B, Sadoshima J (2007) Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circ Res 100:914–922

    Article  CAS  PubMed  Google Scholar 

  • Matsuzaki Y, Nakayama K, Tomita T, Isoda M, Loh DY, Nakauchi H (1997) Role of bcl-2 in the development of lymphoid cells from the hematopoietic stem cell. Blood 89:853–862

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Miller RA, Stutman O (1984) T cell repopulation from functionally restricted splenic progenitors: 10,000-fold expansion documented by using limiting dilution analyses. J Immunol 133:2925–2932

    CAS  PubMed  Google Scholar 

  • Mizushima N, Ohsumi Y, Yoshimori T (2002) Autophagosome formation in mammalian cells. Cell Struct Funct 27:421–429

    Article  PubMed  Google Scholar 

  • Morrissey PJ, Conlon P, Charrier K, Braddy S, Alpert A, Williams D, Namen AE, Mochizuki D (1991) Administration of IL-7 to normal mice stimulates B-lymphopoiesis and peripheral lymphadenopathy. J Immunol 147:561–568

    CAS  PubMed  Google Scholar 

  • Motoyama N, Wang F, Roth KA, Sawa H, Nakayama K, Negishi I, Senju S, Zhang Q, Fujii S et al (1995) Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. Science 267:1506–1510

    Article  CAS  PubMed  Google Scholar 

  • Murali-Krishna K, Altman JD, Suresh M, Sourdive DJ, Zajac AJ, Miller JD, Slansky J, Ahmed R (1998) Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity 8:177–187

    Article  CAS  PubMed  Google Scholar 

  • Murali-Krishna K, Lau LL, Sambhara S, Lemonnier F, Altman J, Ahmed R (1999) Persistence of memory CD8 T cells in MHC class I-deficient mice. Science 286:1377–1381

    Article  CAS  PubMed  Google Scholar 

  • Nakayama K, Nakayama K, Negishi I, Kuida K, Shinkai Y, Louie MC, Fields LE, Lucas PJ, Stewart V, Alt FWet al (1993) Disappearance of the lymphoid system in Bcl-2 homozygous mutant chimeric mice. Science 261:1584–1588

    Article  CAS  PubMed  Google Scholar 

  • Nesic D, Vukmanovic S (1998) MHC class I is required for peripheral accumulation of CD8+ thymic emigrants. J Immunol 160:3705–3712

    CAS  PubMed  Google Scholar 

  • Newton K, Harris AW, Bath ML, Smith KG, Strasser A (1998) A dominant interfering mutant of FADD/MORT1 enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes. EMBO J 17:706–718

    Article  CAS  PubMed  Google Scholar 

  • Newton K, Harris AW, Strasser A (2000) FADD/MORT1 regulates the pre-TCR checkpoint and can function as a tumour suppressor. EMBO J 19:931–941

    Article  CAS  PubMed  Google Scholar 

  • Newton K, Kurts C, Harris AW, Strasser A (2001) Effects of a dominant interfering mutant of FADD on signal transduction in activated T cells. Curr Biol 11:273–276

    Article  CAS  PubMed  Google Scholar 

  • Nguyen LT, McKall-Faienza K, Zakarian A, Speiser DE, Mak TW, Ohashi PS (2000) TNF receptor 1 (TNFR1) and CD95 are not required for T cell deletion after virus infection but contribute to peptide-induced deletion under limited conditions. Eur J Immunol 30:683–688

    Article  CAS  PubMed  Google Scholar 

  • Nowikovsky K, Reipert S, Devenish RJ, Schweyen RJ (2007) Mdm38 protein depletion causes loss of mitochondrial K+/H+ exchange activity, osmotic swelling and mitophagy. Cell Death Differ 14:1647–1656

    Article  CAS  PubMed  Google Scholar 

  • Opferman JT, Letai A, Beard C, Sorcinelli MD, Ong CC, Korsmeyer SJ (2003) Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature 426:671–676

    Article  CAS  PubMed  Google Scholar 

  • Page DM (1999) Cutting edge: thymic selection and autoreactivity are regulated by multiple coreceptors involved in T cell activation. J Immunol 163:3577–3581

    CAS  PubMed  Google Scholar 

  • Page DM, Roberts EM, Peschon JJ, Hedrick SM (1998) TNF receptor-deficient mice reveal striking differences between several models of thymocyte negative selection. J Immunol 160:120–133

    CAS  PubMed  Google Scholar 

  • Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, Packer M, Schneider MD, Levine B (2005) Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122:927–939

    Article  CAS  PubMed  Google Scholar 

  • Pellegrini M, Belz G, Bouillet P, Strasser A (2003) Shutdown of an acute T cell immune response to viral infection is mediated by the proapoptotic Bcl-2 homology 3-only protein Bim. Proc Natl Acad Sci USA 100:14175–14180

    Article  CAS  PubMed  Google Scholar 

  • Pfeffer K, Matsuyama T, Kundig TM, Wakeham A, Kishihara K, Shahinian A, Wiegmann K, Ohashi PS, Kronke M, Mak TW (1993) Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L monocytogenes infection. Cell 73:457–467

    Article  CAS  PubMed  Google Scholar 

  • Plas DR, Rathmell JC, Thompson CB (2002) Homeostatic control of lymphocyte survival: potential origins and implications. Nat Immunol 3:515–521

    Article  CAS  PubMed  Google Scholar 

  • Polic B, Kunkel D, Scheffold A, Rajewsky K (2001) How alpha beta T cells deal with induced TCR alpha ablation. Proc Natl Acad Sci USA 98:8744–8749

    Article  CAS  PubMed  Google Scholar 

  • Priault M, Salin B, Schaeffer J, Vallette FM, di Rago JP, Martinou JC (2005) Impairing the bioenergetic status and the biogenesis of mitochondria triggers mitophagy in yeast. Cell Death Differ 12:1613–1621

    Article  CAS  PubMed  Google Scholar 

  • Pua HH, He YW (2007) Maintaining T lymphocyte homeostasis: another duty of autophagy. Autophagy 3:266–267

    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 204:25–31

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Pyo JO, Jang MH, Kwon YK, Lee HJ, Jun JI, Woo HN, Cho DH, Choi B, Lee H, Kim JHet al (2005) Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death. J Biol Chem 280:20722–20729

    Article  CAS  PubMed  Google Scholar 

  • Qing G, Yan P, Xiao G (2006) Hsp90 inhibition results in autophagy-mediated proteasome-independent degradation of IkappaB kinase (IKK). Cell Res 16:895–901

    Article  CAS  PubMed  Google Scholar 

  • Qing G, Yan P, Qu Z, Liu H, Xiao G (2007) Hsp90 regulates processing of NF-kappaB2 p100 involving protection of NF-kappaB-inducing kinase (NIK) from autophagy-mediated degradation. Cell Res 17:520–530

    Article  CAS  PubMed  Google Scholar 

  • Rathmell JC, Farkash EA, Gao W, Thompson CB (2001) IL-7 enhances the survival and maintains the size of naive T cells. J Immunol 167:6869–6876

    CAS  PubMed  Google Scholar 

  • Rathmell JC, Lindsten T, Zong WX, Cinalli RM, Thompson CB (2002) Deficiency in Bak and Bax perturbs thymic selection and lymphoid homeostasis. Nat Immunol 3:932–939

    Article  CAS  PubMed  Google Scholar 

  • Ravikumar B, Berger Z, Vacher C, O’Kane CJ, Rubinsztein DC (2006) Rapamycin pre-treatment protects against apoptosis. Hum Mol Genet 15:1209–1216

    Article  CAS  PubMed  Google Scholar 

  • Reich A, Korner H, Sedgwick JD, Pircher H (2000) Immune down-regulation and peripheral deletion of CD8 T cells does not require TNF receptor–ligand interactions nor CD95 (Fas, APO-1). Eur J Immunol 30:678–682

    Article  CAS  PubMed  Google Scholar 

  • Reipert S, Berry J, Hughes MF, Hickman JA, Allen TD (1995) Changes of mitochondrial mass in the hemopoietic stem cell line FDCP-mix after treatment with etoposide: a correlative study by multiparameter flow cytometry and confocal and electron microscopy. Exp Cell Res 221:281–288

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez-Enriquez S, Kim I, Currin RT, Lemasters JJ (2006) Tracker dyes to probe mitochondrial autophagy (mitophagy) in rat hepatocytes. Autophagy 2:39–46

    CAS  PubMed  Google Scholar 

  • Sandoval H, Thiagarajan P, Dasgupta SK, Schumacher A, Prchal JT, Chen M, Wang J (2008) Essential role for Nix in autophagic maturation of erythroid cells. Nature 454:232–235

    Article  CAS  PubMed  Google Scholar 

  • Schluns KS, Kieper WC, Jameson SC, Lefrancois L (2000) Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo. Nat Immunol 1:426–432

    Article  CAS  PubMed  Google Scholar 

  • Schmid D, Munz C (2007) Innate and adaptive immunity through autophagy. Immunity 27:11–21

    Article  CAS  PubMed  Google Scholar 

  • Schweers RL, Zhang J, Randall MS, Loyd MR, Li W, Dorsey FC, Kundu M, Opferman JT, Cleveland JL, Miller JL et al (2007) NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci USA 104:19500–19505

    Article  CAS  PubMed  Google Scholar 

  • Seddon B, Zamoyska R (2002) TCR and IL-7 receptor signals can operate independently or synergize to promote lymphopenia-induced expansion of naive T cells. J Immunol 169:3752–3759

    CAS  PubMed  Google Scholar 

  • Seddon B, Tomlinson P, Zamoyska R (2003) Interleukin 7 and T cell receptor signals regulate homeostasis of CD4 memory cells. Nat Immunol 4:680–686

    Article  CAS  PubMed  Google Scholar 

  • Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson CB, Tsujimoto Y (2004) Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol 6:1221–1228

    Article  CAS  PubMed  Google Scholar 

  • Sudo T, Nishikawa S, Ohno N, Akiyama N, Tamakoshi M, Yoshida H, Nishikawa S (1993) Expression and function of the interleukin 7 receptor in murine lymphocytes. Proc Natl Acad Sci USA 90:9125–9129

    Article  CAS  PubMed  Google Scholar 

  • Swain SL, Hu H, Huston G (1999) Class II-independent generation of CD4 memory T cells from effectors. Science 286:1381–1383

    Article  CAS  PubMed  Google Scholar 

  • Takano-Ohmuro H, Mukaida M, Kominami E, Morioka K (2000) Autophagy in embryonic erythroid cells: its role in maturation. Eur J Cell Biol 79:759–764

    Article  CAS  PubMed  Google Scholar 

  • Tamas P, Hawley SA, Clarke RG, Mustard KJ, Green K, Hardie DG, Cantrell DA (2006) Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes. J Exp Med 203:1665–1670

    Article  CAS  PubMed  Google Scholar 

  • Tan JT, Dudl E, LeRoy E, Murray R, Sprent J, Weinberg KI, Surh CD (2001) IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc Natl Acad Sci USA 98:8732–8737

    Article  CAS  PubMed  Google Scholar 

  • Tan JT, Ernst B, Kieper WC, LeRoy E, Sprent J, Surh CD (2002) Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells. J Exp Med 195:1523–1532

    Article  CAS  PubMed  Google Scholar 

  • Terman A, Dalen H, Eaton JW, Neuzil J, Brunk UT (2003) Mitochondrial recycling and aging of cardiac myocytes: the role of autophagocytosis. Exp Gerontol 38:863–876

    Article  CAS  PubMed  Google Scholar 

  • Thorburn J, Moore F, Rao A, Barclay WW, Thomas LR, Grant KW, Cramer SD, Thorburn A (2005) Selective inactivation of a Fas-associated death domain protein (FADD)-dependent apoptosis and autophagy pathway in immortal epithelial cells. Mol Biol Cell 16:1189–1199

    Article  CAS  PubMed  Google Scholar 

  • Thumm M, Egner R, Koch B, Schlumpberger M, Straub M, Veenhuis M, Wolf DH (1994) Isolation of autophagocytosis mutants of Saccharomyces cerevisiae. FEBS Lett 349:275–280

    Article  CAS  PubMed  Google Scholar 

  • Tsukada M, Ohsumi Y (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333:169–174

    Article  CAS  PubMed  Google Scholar 

  • van Oers NS, Killeen N, Weiss A (1994) ZAP-70 is constitutively associated with tyrosine-phosphorylated TCR zeta in murine thymocytes and lymph node T cells. Immunity 1:675–685

    Article  CAS  PubMed  Google Scholar 

  • Veis DJ, Sorenson CM, Shutter JR, Korsmeyer SJ (1993) Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell 75:229–240

    Article  CAS  PubMed  Google Scholar 

  • Vella A, Teague TK, Ihle J, Kappler J, Marrack P (1997) Interleukin 4 (IL-4) or IL-7 prevents the death of resting T cells: stat6 is probably not required for the effect of IL-4. J Exp Med 186:325–330

    Article  CAS  PubMed  Google Scholar 

  • Villunger A, Marsden VS, Zhan Y, Erlacher M, Lew AM, Bouillet P, Berzins S, Godfrey DI, Heath WR, Strasser A (2004) Negative selection of semimature CD4(+)8(–)HSA+ thymocytes requires the BH3-only protein Bim but is independent of death receptor signaling. Proc Natl Acad Sci USA 101:7052–7057

    Article  CAS  PubMed  Google Scholar 

  • Viret C, Wong FS, Janeway CA Jr (1999) Designing and maintaining the mature TCR repertoire: the continuum of self-peptide:self-MHC complex recognition. Immunity 10:559–568

    Article  CAS  PubMed  Google Scholar 

  • Vivien L, Benoist C, Mathis D (2001) T lymphocytes need IL-7 but not IL-4 or IL-6 to survive in vivo. Int Immunol 13:763–768

    Article  CAS  PubMed  Google Scholar 

  • von Freeden-Jeffry U, Solvason N, Howard M, Murray R (1997) The earliest T lineage-committed cells depend on IL-7 for Bcl-2 expression and normal cell cycle progression. Immunity 7:147–154

    Article  CAS  PubMed  Google Scholar 

  • Walsh CM, Wen BG, Chinnaiyan AM, O’Rourke K, Dixit VM, Hedrick SM (1998) A role for FADD in T cell activation and development. Immunity 8:439–449

    Article  CAS  PubMed  Google Scholar 

  • Wang EC, Thern A, Denzel A, Kitson J, Farrow SN, Owen MJ (2001) DR3 regulates negative selection during thymocyte development. Mol Cell Biol 21:3451–3461

    Article  CAS  PubMed  Google Scholar 

  • Watanabe K, Ichinose S, Hayashizaki K, Tsubata T (2008) Induction of autophagy by B cell antigen receptor stimulation and its inhibition by costimulation. Biochem Biophys Res Commun 374:274–281

    Article  CAS  PubMed  Google Scholar 

  • Weant AE, Michalek RD, Khan IU, Holbrook BC, Willingham MC, Grayson JM (2008) Apoptosis regulators Bim and Fas function concurrently to control autoimmunity and CD8+ T cell contraction. Immunity 28:218–230

    Article  CAS  PubMed  Google Scholar 

  • Witherden D, van Oers N, Waltzinger C, Weiss A, Benoist C, Mathis D (2000) Tetracycline-controllable selection of CD4(+) T cells: half-life and survival signals in the absence of major histocompatibility complex class II molecules. J Exp Med 191:355–364

    Article  CAS  PubMed  Google Scholar 

  • Wojciechowski S, Jordan MB, Zhu Y, White J, Zajac AJ, Hildeman DA (2006) Bim mediates apoptosis of CD127(lo) effector T cells and limits T cell memory. Eur J Immunol 36:1694–1706

    Article  CAS  PubMed  Google Scholar 

  • Wullschleger S, Loewith R, Oppliger W, Hall MN (2005) Molecular organization of target of rapamycin complex 2. J Biol Chem 280:30697–30704

    Article  CAS  PubMed  Google Scholar 

  • Yan P, Qing G, Qu Z, Wu CC, Rabson A, Xiao G (2007) Targeting autophagic regulation of NFkappaB in HTLV-I transformed cells by geldanamycin: implications for therapeutic interventions. Autophagy 3:600–603

    CAS  PubMed  Google Scholar 

  • Yu L, Alva A, Su H, Dutt P, Freundt E, Welsh S, Baehrecke EH, Lenardo MJ (2004) Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science 304:1500–1502

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Cado D, Chen A, Kabra NH, Winoto A (1998a) Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mort1. Nature 392:296–300

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Kabra NH, Cado D, Kang C, Winoto A (2001) FADD-deficient T cells exhibit a disaccord in regulation of the cell cycle machinery. J Biol Chem 276:29815–29818

    Article  CAS  PubMed  Google Scholar 

  • Zhang N, He YW (2005) The antiapoptotic protein Bcl-xL is dispensable for the development of effector and memory T lymphocytes. J Immunol 174:6967–6973

    CAS  PubMed  Google Scholar 

  • Zhang N, Hartig H, Dzhagalov I, Draper D, He YW (2005a) The role of apoptosis in the development and function of T lymphocytes. Cell Res 15:749–769

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Sun S, Hwang I, Tough DF, Sprent J (1998b) Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 8:591–599

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Rosenberg S, Wang H, Imtiyaz HZ, Hou YJ, Zhang J (2005b) Conditional Fas-associated death domain protein (FADD): GFP knockout mice reveal FADD is dispensable in thymic development but essential in peripheral T cell homeostasis. J Immunol 175:3033–3044

    CAS  PubMed  Google Scholar 

  • Zhou D, Spector SA (2008) Human immunodeficiency virus type-1 infection inhibits autophagy. AIDS 22:695–699

    Article  CAS  PubMed  Google Scholar 

  • Zinkel S, Gross A, Yang E (2006) BCL2 family in DNA damage and cell cycle control. Cell Death Differ 13:1351–1359

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Immunology, Duke University Medical Center, 3010, Durham, NC, 27710, USA

    Heather H. Pua & You-Wen He

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  1. Heather H. Pua
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  2. You-Wen He
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Correspondence to You-Wen He .

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  1. Southwestern Medical Center, University of Texas, Harry Hines Blvd. 5323, Dallas, 75390-9113, U.S.A.

    Beth Levine

  2. Research Inst. Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita, Osaka, 565-0871, Japan

    Tamotsu Yoshimori

  3. Health Sciences Center, University of New Mexico, Camino de Salud NE., 915, Albuquerque, 87131, U.S.A.

    Vojo Deretic

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Pua, H.H., He, YW. (2009). Autophagy and Lymphocyte Homeostasis. In: Levine, B., Yoshimori, T., Deretic, V. (eds) Autophagy in Infection and Immunity. Current Topics in Microbiology and Immunology, vol 335. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00302-8_4

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