T-cell-mediated immunity and the role of TRAIL in sepsis-induced immunosuppression

Critical Reviews in Immunology

Volumn 33, Issue 1, 2013, Pages 23-40

  Condotta, Stephanie A ^a   Cabrera Perez, Javier ^b   Badovinac, Vladimir P ^a,c   Griffith, Thomas S ^b,d,e  

^a UNIVERSITY OF IOWA   (United States)

^b UNIVERSITY OF MINNESOTA   (United States)

^c UNIVERSITY OF IOWA   (United States)

^d UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^e VA MEDICAL CENTER   (United States)

Author keywords

Apoptosis; CD8 T cells; Homeostatic proliferation; Sepsis; Tolerance; TRAIL

Indexed keywords

CASPASE 3; DROTRECOGIN; GAMMA INTERFERON; HERMES ANTIGEN; INTERLEUKIN 1; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR BETA; LYMPHOCYTE FUNCTION ASSOCIATED ANTIGEN 1; RECOMBINANT INTERLEUKIN 15; RECOMBINANT INTERLEUKIN 7; T LYMPHOCYTE RECEPTOR; THROMBOCYTE ACTIVATING FACTOR; TOLL LIKE RECEPTOR 4; TUMOR NECROSIS FACTOR; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND;

ANTIGEN SPECIFICITY; APOPTOSIS; ARTICLE; CD8+ T LYMPHOCYTE; CELL COMPARTMENTALIZATION; CELL SURVIVAL; CELLULAR IMMUNITY; ENZYME ACTIVITY; HOMEOSTASIS; HOSPITAL INFECTION; HUMAN; IMMUNE DEFICIENCY; IMMUNOCOMPETENT CELL; IMMUNOLOGICAL TOLERANCE; INFECTION CONTROL; LYMPHOCYTE COUNT; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE PROLIFERATION; LYMPHOCYTE SUBPOPULATION; MEMORY T LYMPHOCYTE; MORTALITY; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; SECONDARY INFECTION; SEPSIS;

EID: 84875079438     PISSN: 10408401     EISSN: None     Source Type: Journal    
DOI: 10.1615/CritRevImmunol.2013006721     Document Type: Article

References (128)

1. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101:1644-55.
2. Lever A, Mackenzie I. Sepsis: definition, epidemiology, and diagnosis. BMJ. 2007;335:879-883.
3. Geroulanos S, Douka ET. Historical perspective of the word "sepsis". Intensive Care Med. 2006;32:2077.
4. Baue AE. Sepsis research: what did we do wrong? What would Semmelweis do today? Shock. 2001;16:1-8.
5. Martí-Carvajal AJ, Solà I, Gluud C, Lathyris D, Cardona AF. Human recombinant protein C for severe sepsis and septic shock in adult and paediatric patients. Cochrane Database Syst Rev. 2012;3:CD004388.
6. Wang HE, Shapiro NI, Angus DC, Yealy DM. National estimates of severe sepsis in United States emergency departments. Crit Care Med. 2007;35:1928-36.
7. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348:1546-54.
8. Iwashyna TJ, Netzer G, Langa KM, Cigolle C. Spurious inferences about long-term outcomes: the case of severe sepsis and geriatric conditions. Am J Respir Crit Care Med. 2012;185:835-41.
9. Destarac LA, Ely EW. Sepsis in older patients: an emerging concern in critical care. Adv Sepsis. 2002;2:12-22.
10. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303-10.
11. Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304:1787-94.
12. Angus DC, Pereira CA, Silva E. Epidemiology of severe sepsis around the world. Endocr Metab Immune Disord Drug Targets. 2006;6:207-12.
13. Lee H, Doig CJ, Ghali WA, Donaldson C, Johnson D, Manns B. Detailed cost analysis of care for survivors of severe sepsis. Crit Care Med. 2004;32:981-5.
14. Heyland DK, Hopman W, Coo H, Tranmer J, McColl MA. Long-term health-related quality of life in survivors of sepsis. Short Form 36: a valid and reliable measure of health-related quality of life. Crit Care Med. 2000;28:3599-3605.
15. Berger MM, Chiolero RL. Antioxidant supplementation in sepsis and systemic inflammatory response syndrome. Crit Care Med. 2007;35:S584-90.
16. Pinsky MR, Vincent JL, Deviere J, Alegre M, Kahn RJ, Dupont E. Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality. Chest. 1993;103:565-75.
17. Cohen J. The immunopathogenesis of sepsis. Nature. 2002;420:885-91.
18. Hack CE, De Groot ER, Felt-Bersma RJ, Nuijens JH, Strack Van Schijndel RJ, Eerenberg-Belmer AJ, Thijs LG, Aarden LA. Increased plasma levels of interleukin-6 in sepsis. Blood. 1989;74:1704-1710.
19. Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. New Engl J Med. 2001;345:588-95.
20. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20:864-74.
21. Bone RC. Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med. 1996;24:1125-8.
22. Freeman BD, Nathanson C. Clinical trials in sepsis and septic shock in 1994 and 1995. Curr Opin Crit Care. 1995;1:349-57.
23. Baker CC, Miller CL, Trunkey DD, Lim RC Jr. Identity of mononuclear cells which compromise the resistance of trauma patients. J Surg Res. 1979;26:478-87.
24. Hansbrough JF, Bender EM, Zapata-Sirvent R, Anderson J. Altered helper and suppressor lymphocyte populations in surgical patients. A measure of postoperative immunosuppression. Am J Surg. 1984;148:303-07.
25. Meakins JL, Pietsch JB, Bubenick O, Kelly R, Rode H, Gordon J, MacLean LD. Delayed hypersensitivity: indicator of acquired failure of host defenses in sepsis and trauma. Ann Surg. 1977;186:241-50.
26. Munster AM. Post-traumatic immunosuppression is due to activation of suppressor T cells. Lancet. 1976;1:1329-30.
27. Hotchkiss RS, Karl IE. Endothelial cell apoptosis in sepsis: a case of habeas corpus? Crit Care Med. 2004;32:901-902.
28. Moldawer LL. Organ apoptosis in the septic patient: a potential therapeutic target? Crit Care Med. 1999;27:1381-2.
29. Castelino DJ, McNair P, Kay TW. Lymphocytopenia in a hospital population--what does it signify? Aust NZ J Med. 1997;27:170-4.
30. Abraham E. Physiologic stress and cellular ischemia: relationship to immunosuppression and susceptibility to infection. Crit Care Med. 1991;19:613-8.
31. Dinarello CA, Gelfand JA, Wolff SM. Anticytokine strategies in the treatment of the systemic inflammatory response syndrome. JAMA. 1993;269:1829-35.
32. Abraham E, Glauser MP, Butler T, Garbino J, Gelmont D, Laterre PF, Kudsk K, Bruining HA, Otto C, Tobin E, Zwingelstein C, Lesslauer W, Leighton A. p55 Tumor necrosis factor receptor fusion protein in the treatment of patients with severe sepsis and septic shock. A randomized controlled multicenter trial. Ro 45-2081 Study Group. JAMA. 1997;277:1531-8.
33. Abraham E, Laterre PF, Garbino J, Pingleton S, Butler T, Dugernier T, Margolis B, Kudsk K, Zimmerli W, Anderson P, Reynaert M, Lew D, Lesslauer W, Passe S, Cooper P, Burdeska A, Modi M, Leighton A, Salgo M, Van der Auwera P. Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebocontrolled, multicenter phase III trial with 1,342 patients. Crit Care Med. 2001;29:503-10.
34. Fisher CJ Jr, Agosti JM, Opal SM, Lowry SF, Balk RA, Sadoff JC, Abraham E, Schein RM, Benjamin E. Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group. New Engl J Med. 1996;334:1697-1702.
35. Dhainaut JF, Tenaillon A, Le Tulzo Y, Schlemmer B, Solet JP, Wolff M, Holzapfel L, Zeni F, Dreyfuss D, Mira JP, de Vathaire F, Guinot P, Group tBSS. Platelet-activating factor receptor antagonist BN 52021 in the treatment of severe sepsis: a randomized, double-blind, placebo-controlled, multicenter clinical trial. BN 52021 Sepsis Study Group. Crit Care Med. 1994;22:1720-8.
36. Fisher CJ, Jr., Dhainaut JF, Opal SM, Pribble JP, Balk RA, Slotman GJ, Iberti TJ, Rackow EC, Shapiro MJ, Greenman RL, Reines HD, Shelly MP, Thompson BW, LaBrecque JF, Catalano MA, Knaus WA, Sadoff JC, Group ftPIr-rSSS. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. JAMA. 1994;271:1836-43.
37. Fisher CJ Jr, Slotman GJ, Opal SM, Pribble JP, Bone RC, Emmanuel G, Ng D, Bloedow DC, Catalano MA. Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open-label, placebo-controlled multicenter trial. Crit Care Med. 1994;22:12-21.
38. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr. Efficacy and safety of recombinant human activated protein C for severe sepsis. New Engl J Med. 2001;344:699-709.
39. Bernard GR, Margolis BD, Shanies HM, Ely EW, Wheeler AP, Levy H, Wong K, Wright TJ. Extended evaluation of recombinant human activated protein C United States Trial (ENHANCE US): a single-arm, phase 3B, multicenter study of drotrecogin alfa (activated) in severe sepsis. Chest. 2004;125:2206-16.
40. Carlet J. Drotrecogin alfa (activated) administration: too many subgroups. Crit Care Med. 2003;31:2564; author reply 2564-5.
41. Green C, Dinnes J, Takeda A, Shepherd J, Hartwell D, Cave C, Payne E, Cuthbertson BH. Clinical effectiveness and cost-effectiveness of drotrecogin alfa (activated) (Xigris) for the treatment of severe sepsis in adults: a systematic review and economic evaluation. Health Technol Assess. 2005;9:1-126, iii-iv.
42. Tidswell M, Tillis W, Larosa SP, Lynn M, Wittek AE, Kao R, Wheeler J, Gogate J, Opal SM. Phase 2 trial of eritoran tetrasodium (E5564), a toll-like receptor 4 antagonist, in patients with severe sepsis. Crit Care Med. 2010;38:72-83.
43. Levy MM, Artigas A, Phillips GS, Rhodes A, Beale R, Osborn T, Vincent JL, Townsend S, Lemeshow S, Dellinger RP. Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe: a prospective cohort study. Lancet Infect Dis. 2012;12:919-24.
44. Angus DC, Wax RS. Epidemiology of sepsis: an update. Crit Care Med. 2001;29:S109-16.
45. Brun-Buisson C. The epidemiology of the systemic inflammatory response. Intens Care Med. 2000;26(Suppl 1):S64-74.
46. Sands KE, Bates DW, Lanken PN, Graman PS, Hibberd PL, Kahn KL, Parsonnet J, Panzer R, Orav EJ, Snydman DR, Black E, Schwartz JS, Moore R, Johnson BL Jr, Platt R. Epidemiology of sepsis syndrome in 8 academic medical centers. JAMA. 1997;278:234-40.
47. Sasse KC, Nauenberg E, Long A, Anton B, Tucker HJ, Hu TW. Long-term survival after intensive care unit admission with sepsis. Crit Care Med. 1995;23:1040-7.
48. Quartin AA, Schein RM, Kett DH, Peduzzi PN. Magnitude and duration of the effect of sepsis on survival. Department of Veterans Affairs Systemic Sepsis Cooperative Studies Group. JAMA. 1997;277:1058-63.
49. Perl TM, Dvorak L, Hwang T, Wenzel RP. Long-term survival and function after suspected gram-negative sepsis. JAMA. 1995;274:338-45.
50. Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM, Buchman TG, Karl IE. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med. 1999;27:1230-51.
51. Hotchkiss RS, Tinsley KW, Swanson PE, Schmieg RE Jr, Hui JJ, Chang KC, Osborne DF, Freeman BD, Cobb JP, Buchman TG, Karl IE. Sepsisinduced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol. 2001;166:6952-63.
52. Le Tulzo Y, Pangault C, Gacouin A, Guilloux V, Tribut O, Amiot L, Tattevin P, Thomas R, Fauchet R, Drenou B. Early circulating lymphocyte apoptosis in human septic shock is associated with poor outcome. Shock. 2002;18:487-94.
53. Hotchkiss RS, Osmon SB, Chang KC, Wagner TH, Coopersmith CM, Karl IE. Accelerated lymphocyte death in sepsis occurs by both the death receptor and mitochondrial pathways. J Immunol. 2005;174:5110-8.
54. Rittirsch D, Huber-Lang MS, Flierl MA, Ward PA. Immunodesign of experimental sepsis by cecal ligation and puncture. Nat Protoc. 2009;4:31-6.
55. Gurung P, Rai D, Condotta SA, Babcock JC, Badovinac VP, Griffith TS. Immune unresponsiveness to secondary heterologous bacterial infection after sepsis induction is TRAIL dependent. J Immunol. 2011;187:2148-54.
56. Unsinger J, Kazama H, McDonough JS, Hotchkiss RS, Ferguson TA. Differential lymphopeniainduced homeostatic proliferation for CD4+ and CD8+ T cells following septic injury. J Leuk Biol. 2009;85:382-90.
57. Unsinger J, Kazama H, McDonough JS, Griffith TS, Hotchkiss RS, Ferguson TA. Sepsis-induced apoptosis leads to active suppression of delayedtype hypersensitivity by CD8+ regulatory T cells through a TRAIL-dependent mechanism. J Immunol. 2010;184:6766-72.
58. Condotta SA, Rai D, James BR, Griffith TS, Badovinac VP. Sustained and incomplete recovery of naive CD8+ T cell precursors after sepsis contributes to impaired CD8+ T cell responses to infection. J Immunol. 2013;190:1991-2000.
59. Harty JT, Tvinnereim AR, White DW. CD8+ T cell effector mechanisms in resistance to infection. Annu Rev Immunol. 2000;18:275-308.
60. Harty JT, Badovinac VP. Shaping and reshaping CD8+ T-cell memory. Nat Rev Immunol. 2008;8:107-19.
61. Butler NS, Harty JT. The role of inflammation in the generation and maintenance of memory T cells. Adv Exp Med Biol. 2010;684:42-56.
62. Curtsinger JM, Schmidt CS, Mondino A, Lins DC, Kedl RM, Jenkins MK, Mescher MF. Inflammatory cytokines provide a third signal for activation of naive CD4+ and CD8+ T cells. J Immunol. 1999;162:3256-62.
63. Curtsinger JM, Valenzuela JO, Agarwal P, Lins D, Mescher MF. Type I IFNs provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation. J Immunol. 2005;174:4465-9.
64. Mescher MF, Curtsinger JM, Agarwal P, Casey KA, Gerner M, Hammerbeck CD, Popescu F, Xiao Z. Signals required for programming effector and memory development by CD8+ T cells. Immunol Rev. 2006;211:81-92.
65. Haring JS, Badovinac VP, Harty JT. Inflaming the CD8+ T cell response. Immunity. 2006;25:19-29.
66. Butler NS, Nolz JC, Harty JT. Immunologic considerations for generating memory CD8 T cells through vaccination. Cell Microbiol. 2011;13:925-33.
67. Casrouge A, Beaudoing E, Dalle S, Pannetier C, Kanellopoulos J, Kourilsky P. Size estimate of the alpha beta TCR repertoire of naive mouse splenocytes. J Immunol. 2000;164:5782-7.
68. Blattman JN, Antia R, Sourdive DJ, Wang X, Kaech SM, Murali-Krishna K, Altman JD, Ahmed R. Estimating the precursor frequency of naive antigen-specific CD8 T cells. J Exp Med. 2002;195:657-64.
69. Moon JJ, Chu HH, Pepper M, McSorley SJ, Jameson SC, Kedl RM, Jenkins MK. Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude. Immunity. 2007;27:203-13.
70. Obar JJ, Khanna KM, Lefrancois L. Endogenous naive CD8+ T cell precursor frequency regulates primary and memory responses to infection. Immunity. 2008;28:859-69.
71. Jenkins MK, Moon JJ. The role of naive T cell precursor frequency and recruitment in dictating immune response magnitude. J Immunol. 2012;188:4135-40.
72. Nikolich-Zugich J, Slifka MK, Messaoudi I. The many important facets of T-cell repertoire diversity. Nat Rev Immunol. 2004;4:123-32.
73. Badovinac VP, Harty JT. CD8(+) T-cell homeostasis after infection: setting the 'curve'. Microbes Infect. 2002;4:441-7.
74. Butz EA, Bevan MJ. Massive expansion of antigen-specific CD8+ T cells during an acute virus infection. Immunity. 1998;8:167-75.
75. Harty JT, Badovinac VP. Influence of effector molecules on the CD8(+) T cell response to infection. Curr Opin Immunol. 2002;14:360-5.
76. Badovinac VP, Harty JT. Programming, demarcating, and manipulating CD8+ T-cell memory. Immunol Rev. 2006;211:67-80.
77. Kotturi MF, Scott I, Wolfe T, Peters B, Sidney J, Cheroutre H, von Herrath MG, Buchmeier MJ, Grey H, Sette A. Naive precursor frequencies and MHC binding rather than the degree of epitope diversity shape CD8+ T cell immunodominance. J Immunol. 2008;181:2124-33.
78. Blackman MA, Woodland DL. The narrowing of the CD8 T cell repertoire in old age. Curr Opin Immunol. 2011;23:537-42.
79. Yager EJ, Ahmed M, Lanzer K, Randall TD, Woodland DL, Blackman MA. Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus. J Exp Med. 2008;205:711-23.
80. Lee JB, Oelke M, Ramachandra L, Canaday DH, Schneck JP. Decline of influenza-specific CD8+ T cell repertoire in healthy geriatric donors. Immun Ageing. 2011;8:6.
81. Callahan JE, Kappler JW, Marrack P. Unexpected expansions of CD8-bearing cells in old mice. J Immunol. 1993;151:6657-69.
82. Messaoudi I, Lemaoult J, Guevara-Patino JA, Metzner BM, Nikolich-Zugich J. Age-related CD8 T cell clonal expansions constrict CD8 T cell repertoire and have the potential to impair immune defense. J Exp Med. 2004;200:1347-58.
83. Cicin-Sain L, Brien JD, Uhrlaub JL, Drabig A, Marandu TF, Nikolich-Zugich J. Cytomegalovirus infection impairs immune responses and accentuates T-cell pool changes observed in mice with aging. PLoS Pathog. 2012;8:e1002849.
84. Kaech SM, Wherry EJ, Ahmed R. Effector and memory T-cell differentiation: implications for vaccine development. Nat Rev Immunol. 2002;2:251-62.
85. Kedzierska K, La Gruta NL, Turner SJ, Doherty PC. Establishment and recall of CD8+ T-cell memory in a model of localized transient infection. Immunol Rev. 2006;211:133-45.
86. Hikono H, Kohlmeier JE, Ely KH, Scott I, Roberts AD, Blackman MA, Woodland DL. T-cell memory and recall responses to respiratory virus infections. Immunol Rev. 2006;211:119-32.
87. Rai D, Pham NL, Harty JT, Badovinac VP. Tracking the total CD8 T cell response to infection reveals substantial discordance in magnitude and kinetics between inbred and outbred hosts. J Immunol. 2009;183:7672-81.
88. Cheung KP, Yang E, Goldrath AW. Memory-like CD8+ T cells generated during homeostatic proliferation defer to antigen-experienced memory cells. J Immunol. 2009;183:3364-72.
89. Jameson SC. Maintaining the norm: T-cell homeostasis. Nat Rev Immunol. 2002;2:547-56.
90. Takada K, Jameson SC. Naive T cell homeostasis: from awareness of space to a sense of place. Nat Rev Immunol. 2009;9:823-32.
91. Johnson LD, Jameson SC. Self-specific CD8+ T cells maintain a semi-naive state following lymphopenia-induced proliferation. J Immunol. 2010;184:5604-11.
92. Kieper WC, Jameson SC. Homeostatic expansion and phenotypic conversion of naive T cells in response to self peptide/MHC ligands. Proc Natl Acad Sci U S A. 1999;96:13306-11.
93. Murali-Krishna K, Ahmed R. Cutting edge: naive T cells masquerading as memory cells. J Immunol. 2000;165:1733-7.
94. Cho BK, Rao VP, Ge Q, Eisen HN, Chen J. Homeostasis-stimulated proliferation drives naive T cells to differentiate directly into memory T cells. J Exp Med. 2000;192:549-56.
95. Goldrath AW, Bogatzki LY, Bevan MJ. Naive T cells transiently acquire a memory-like phenotype during homeostasis-driven proliferation. J Exp Med. 2000;192:557-64.
96. Hamilton SE, Wolkers MC, Schoenberger SP, Jameson SC. The generation of protective memory-like CD8+ T cells during homeostatic proliferation requires CD4+ T cells. Nat Immunol. 2006;7:475-81.
97. Zamai L, Ahmad M, Bennett IM, Azzoni L, Alnemri ES, Perussia B. Natural killer (NK) cellmediated cytotoxicity: differential use of TRAIL and Fas ligand by immature and mature primary human NK cells. J Exp Med. 1998;88:2375-80.
98. Schoenberger SP, Toes RE, van der Voort EI, Offringa R, Melief CJ. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature. 1998;393:480-3.
99. Albert ML, Jegathesan M, Darnell RB. Dendritic cell maturation is required for the crosstolerization of CD8+ T cells. Nat Immunol. 2001;2:1010-7.
100. +T-cell memory via TRAILmediated activation-induced cell death. Nature. 2005;434:88-93.
101. Wolkers MC, Gerlach C, Arens R, Janssen EM, Fitzgerald P, Schumacher TN, Medema JP, Green DR, Schoenberger SP. Nab2 regulates secondary CD8+ T-cell responses through control of TRAIL expression. Blood. 2012;119:798-804.
102. Wolkers MC, Bensinger SJ, Green DR, Schoenberger SP, Janssen EM. Interleukin-2 rescues helpless effector CD8+ T cells by diminishing the susceptibility to TRAIL mediated death. Immunol Lett. 2011;139:25-32.
103. Ernst B, Lee DS, Chang JM, Sprent J, Surh CD. The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery. Immunity. 1999;11:173-81.
104. La Gruta NL, Driel IR, Gleeson PA. Peripheral T cell expansion in lymphopenic mice results in a restricted T cell repertoire. Eur J Immunol. 2000;30:3380-6.
105. Prlic M, Jameson SC. Homeostatic expansion versus antigen-driven proliferation: common ends by different means? Microbes Infect. 2002;4:531-7.
106. Khoruts A, Fraser JM. A causal link between lymphopenia and autoimmunity. Immunol Lett. 2005;98:23-31.
107. Krupica T Jr, Fry TJ, Mackall CL. Autoimmunity during lymphopenia: a two-hit model. Clin Immunol. 2006;120:121-8.
108. Debatin KM. Apoptosis pathways in cancer and cancer therapy. Cancer Immunol Immunother. 2004;53:153-9.
109. Hotchkiss RS, Nicholson DW. Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol. 2006;6:813-22.
110. Green DR, Ferguson T, Zitvogel L, Kroemer G. Immunogenic and tolerogenic cell death. Nat Rev Immunol. 2009;9:353-63.
111. Hotchkiss RS, Nicholson DW. Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol. 2006;6:813-22.
112. Hotchkiss RS, Swanson PE, Knudson CM, Chang KC, Cobb JP, Osborne DF, Zollner KM, Buchman TG, Korsmeyer SJ, Karl IE. Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis. J Immunol. 1999;162:4148-56.
113. Unsinger J, McGlynn M, Kasten KR, Hoekzema AS, Watanabe E, Muenzer JT, McDonough JS, Tschoep J, Ferguson TA, McDunn JE, Morre M, Hildeman DA, Caldwell CC, Hotchkiss RS. IL-7 promotes T cell viability, trafficking, and functionality and improves survival in sepsis. J Immunol. 2010;184:3768-79.
114. Inoue S, Unsinger J, Davis CG, Muenzer JT, Ferguson TA, Chang K, Osborne DF, Clark AT, Coopersmith CM, McDunn JE, Hotchkiss RS. IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis. J Immunol. 2010;184:1401-9.
115. Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/ paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest. 1998;101:890-8.
116. Chen W, Frank ME, Jin W, Wahl SM. TGFbeta released by apoptotic T cells contributes to an immunosuppressive milieu. Immunity. 2001;14:715-5.
117. Gao Y, Herndon JM, Zhang H, Griffith TS, Ferguson TA. Antiinflammatory effects of CD95 ligand (FasL)-induced apoptosis. J Exp Med. 1998;188:887-96.
118. Steinman RM, Turley S, Mellman I, Inaba K. The induction of tolerance by dendritic cells that have captured apoptotic cells. J Exp Med. 2000;191:411-6.
119. Green DR, Beere HM. Apoptosis. Gone but not forgotten. Nature. 2000;405:28-9.
120. Hotchkiss RS, Chang KC, Grayson MH, Tinsley KW, Dunne BS, Davis CG, Osborne DF, Karl IE. Adoptive transfer of apoptotic splenocytes worsens survival, whereas adoptive transfer of necrotic splenocytes improves survival in sepsis. Proc Natl Acad Sci U S A. 2003;100:6724-9.
121. Schwartz RH. T cell anergy. Annu Rev Immunol. 2003;21:305-34.
122. +T cells produce active immune unresponsiveness. J Immunol. 2002;168:5589-95.
123. Gurung P, Kucaba TA, Schoenberger SP, Ferguson TA, Griffith TS. TRAIL-expressing CD8+ T cells mediate tolerance following soluble peptideinduced peripheral T cell deletion. J Leukoc Biol. 2010;88:1217-25.
124. +T cells that produce TRAIL. J Immunol. 2007;178:2679-87.
125. Griffith TS, Brincks EL, Gurung P, Kucaba TA, Ferguson TA. Systemic immunological tolerance to ocular antigens is mediated by TRAIL-expressing CD8+ T cells. J Immunol. 2011;186:791-8.
126. Battisto JR, Bloom BR. Dual immunological unresponsiveness induced by cell membrane coupled hapten or antigen. Nature. 1966;212:156-7.
127. Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA, Goodwin RG. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity. 1995;3:673-82.
128. Sedger LM, Glaccum MB, Schuh JC, Kanaly ST, Williamson E, Kayagaki N, Yun T, Smolak P, Le T, Goodwin R, Gliniak B. Characterization of the in vivo function of TNF-alpha-related apoptosisinducing ligand, TRAIL/Apo2L, using TRAIL/ Apo2L gene-deficient mice. Eur J Immunol. 2002;32:2246-54.