Chronic critical illness from sepsis is associated with an enhanced TCR response

Journal of Immunology

Volumn 198, Issue 12, 2017, Pages 4781-4791

  Borken, Farina ^a   Markwart, Robby ^a   Requardt, Robert P ^a   Schubert, Katja ^a   Spacek, Michal ^b   Verner, Miroslav ^b   Rückriem, Stefan ^b   Scherag, André ^a   Oehmichen, Frank ^b   Brunkhorst, Frank M ^a   Rubio, Ignacio ^a  

^a JENA UNIVERSITY HOSPITAL   (Germany)

^b Klinik Bavaria in Kreischa GmbH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CD28 ANTIGEN; CD3 ANTIGEN; CD40 LIGAND; CD69 ANTIGEN; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR ALPHA; LAT PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; NUCLEAR RECEPTOR NUR77; PHOSPHOLIPASE C GAMMA; PROGRAMMED DEATH 1 RECEPTOR; PROTEIN KINASE B; T LYMPHOCYTE RECEPTOR; LYMPHOCYTE ANTIGEN RECEPTOR; PROGRAMMED DEATH 1 LIGAND 1;

ADULT; AGED; ARTICLE; ARTIFICIAL VENTILATION; BLOOD SAMPLING; CELL ASSAY; CELL ISOLATION; CHRONIC DISEASE; CLINICAL ARTICLE; CONTROLLED STUDY; CRITICAL ILLNESS; CYTOKINE PRODUCTION; DISEASE SEVERITY; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; FLOW CYTOMETRY; HUMAN; HUMAN CELL; IMMUNE DEFICIENCY; IMMUNE RESPONSE; IMMUNOPHENOTYPING; LONG TERM CARE; LYMPHOCYTE FUNCTION; MALE; MIDDLE AGED; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; RENAL REPLACEMENT THERAPY; SEPSIS; SIGNAL TRANSDUCTION; T LYMPHOCYTE; CLASSIFICATION; FEMALE; GENETICS; IMMUNOLOGY; IMMUNOSUPPRESSIVE TREATMENT; LYMPHOCYTE ACTIVATION; METABOLISM; PHOSPHORYLATION;

AGED; ANTIGENS, CD274; CRITICAL ILLNESS; FEMALE; FLOW CYTOMETRY; HUMANS; IMMUNOPHENOTYPING; IMMUNOSUPPRESSION; LONG-TERM CARE; LYMPHOCYTE ACTIVATION; MALE; MIDDLE AGED; PHOSPHORYLATION; RECEPTORS, ANTIGEN, T-CELL; RENAL REPLACEMENT THERAPY; RESPIRATION, ARTIFICIAL; SEPSIS; SIGNAL TRANSDUCTION; T-LYMPHOCYTES;

EID: 85020412096     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1700142     Document Type: Article

References (73)

1. Ward, P. A. 2011. Immunosuppression in sepsis. JAMA 306: 2618-2619.
2. Tisoncik, J. R., M. J. Korth, C. P. Simmons, J. Farrar, T. R. Martin, and M. G. Katze. 2012. Into the eye of the cytokine storm. Microbiol. Mol. Biol. Rev. 76: 16-32.
3. London, N. R., W. Zhu, F. A. Bozza, M. C. Smith, D. M. Greif, L. K. Sorensen, L. Chen, Y. Kaminoh, A. C. Chan, S. F. Passi, et al. 2010. Targeting Robo4- dependent Slit signaling to survive the cytokine storm in sepsis and influenza. Sci. Transl. Med. 2: 23ra19.
4. Fry, D. E. 2012. Sepsis, systemic inflammatory response, and multiple organ dysfunction: the mystery continues. Am. Surg. 78: 1-8.
5. Qiu, P., X. Cui, A. Barochia, Y. Li, C. Natanson, and P. Q. Eichacker. 2011. The evolving experience with therapeutic TNF inhibition in sepsis: considering the potential influence of risk of death. Expert Opin. Investig. Drugs 20: 1555-1564.
6. Cohen, J., S. Opal, and T. Calandra. 2012. Sepsis studies need new direction. Lancet Infect. Dis. 12: 503-505.
7. Giamarellos-Bourboulis, E. J. 2013. Failure of treatments based on the cytokine storm theory of sepsis: time for a novel approach. Immunotherapy 5: 207-209.
8. Angus, D. C. 2011. The search for effective therapy for sepsis: back to the drawing board? JAMA 306: 2614-2615.
9. Hotchkiss, R. S., G. Monneret, and D. Payen. 2013. Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach. Lancet Infect. Dis. 13: 260-268.
10. Otto, G. P., M. Sossdorf, R. A. Claus, J. Rödel, K. Menge, K. Reinhart, M. Bauer, and N. C. Riedemann. 2011. The late phase of sepsis is characterized by an increased microbiological burden and death rate. Crit. Care 15: R183.
11. Kalb, T. H., and S. Lorin. 2002. Infection in the chronically critically ill: unique risk profile in a newly defined population. Crit. Care Clin. 18: 529-552.
12. Walton, A. H., J. T. Muenzer, D. Rasche, J. S. Boomer, B. Sato, B. H. Brownstein, A. Pachot, T. L. Brooks, E. Deych, W. D. Shannon, et al. 2014. Reactivation of multiple viruses in patients with sepsis. PLoS One 9: e98819.
13. Venet, F., A. P. Foray, A. Villars-Mechin, C. Malcus, F. Poitevin-Later, A. Lepape, and G. Monneret. 2012. IL-7 restores lymphocyte functions in septic patients. J. Immunol. 189: 5073-5081.
14. De, A. K., K. Kodys, J. C. Puyana, G. Fudem, J. Pellegrini, and C. L. Miller- Graziano. 1997. Only a subset of trauma patients with depressed mitogen responses have true T cell dysfunctions. Clin. Immunol. Immunopathol. 82: 73-82.
15. Pellegrini, J. D., A. K. De, K. Kodys, J. C. Puyana, R. K. Furse, and C. Miller- Graziano. 2000. Relationships between T lymphocyte apoptosis and anergy following trauma. J. Surg. Res. 88: 200-206.
16. Heidecke, C. D., H. Weighardt, T. Hensler, H. Bartels, and B. Holzmann. 2000. Immune paralysis of T-lymphocytes and monocytes in postoperative abdominal sepsis. Correlation of immune function with survival. Chirurg. 71: 159-165.
17. Drewry, A. M., N. Samra, L. P. Skrupky, B. M. Fuller, S. M. Compton, and R. S. Hotchkiss. 2014. Persistent lymphopenia after diagnosis of sepsis predicts mortality. Shock 42: 383-391.
18. Inoue, S., K. Suzuki, Y. Komori, Y. Morishita, K. Suzuki-Utsunomiya, K. Hozumi, S. Inokuchi, and T. Sato. 2014. Persistent inflammation and T cell exhaustion in severe sepsis in the elderly. Crit. Care 18: R130.
19. Boomer, J. S., K. To, K. C. Chang, O. Takasu, D. F. Osborne, A. H. Walton, T. L. Bricker, S. D. Jarman, II, D. Kreisel, A. S. Krupnick, et al. 2011. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA 306: 2594-2605.
20. Hotchkiss, R. S., and E. R. Sherwood. 2015. Immunology. Getting sepsis therapy right. Science 347: 1201-1202.
21. Markwart, R., S. A. Condotta, R. P. Requardt, F. Borken, K. Schubert, C. Weigel, M. Bauer, T. S. Griffith, M. Forster, F. M. Brunkhorst, et al. 2014. Immunosuppression after sepsis: systemic inflammation and sepsis induce a loss of naive T-cells but no enduring cell-autonomous defects in T-cell function. PLoS One 9: e115094.
22. Condotta, S. A., D. Rai, B. R. James, T. S. Griffith, and V. P. Badovinac. 2013. Sustained and incomplete recovery of naive CD8+ T cell precursors after sepsis contributes to impaired CD8+ T cell responses to infection. J. Immunol. 190: 1991-2000.
23. de Jong, H. K., T. van der Poll, and W. J. Wiersinga. 2010. The systemic proinflammatory response in sepsis. J. Innate Immun. 2: 422-430.
24. Bath, P. M., and R. J. Butterworth. 1996. Platelet size: measurement, physiology and vascular disease. Blood Coagul. Fibrinolysis 7: 157-161.
25. Papanas, N., G. Symeonidis, E. Maltezos, G. Mavridis, E. Karavageli, T. Vosnakidis, and G. Lakasas. 2004. Mean platelet volume in patients with type 2 diabetes mellitus. Platelets 15: 475-478.
26. Babu, E., and D. Basu. 2004. Platelet large cell ratio in the differential diagnosis of abnormal platelet counts. Indian J. Pathol. Microbiol. 47: 202-205.
27. Bone, R. C. 1992. Inhibitors of complement and neutrophils: a critical evaluation of their role in the treatment of sepsis. Crit. Care Med. 20: 891-898.
28. Cabrera-Perez, J., S. A. Condotta, V. P. Badovinac, and T. S. Griffith. 2014. Impact of sepsis on CD4 T cell immunity. J. Leukoc. Biol. 96: 767-777.
29. Goldrath, A. W., L. Y. Bogatzki, and M. J. Bevan. 2000. Naive T cells transiently acquire a memory-like phenotype during homeostasis-driven proliferation. J. Exp. Med. 192: 557-564.
30. Parel, Y., and C. Chizzolini. 2004. CD4+ CD8+ double positive (DP) T cells in health and disease. Autoimmun. Rev. 3: 215-220.
31. Dutton, R. W., L. M. Bradley, and S. L. Swain. 1998. T cell memory. Annu. Rev. Immunol. 16: 201-223.
32. Monneret, G., A. L. Debard, F. Venet, J. Bohe, O. Hequet, J. Bienvenu, and A. Lepape. 2003. Marked elevation of human circulating CD4+CD25+ regulatory T cells in sepsis-induced immunoparalysis. Crit. Care Med. 31: 2068-2071.
33. Venet, F., A. Pachot, A. L. Debard, J. Bohe, J. Bienvenu, A. Lepape, and G. Monneret. 2004. Increased percentage of CD4+CD25+ regulatory T cells during septic shock is due to the decrease of CD4+CD25- lymphocytes. Crit. Care Med. 32: 2329-2331.
34. Cao, C., T. Ma, Y. F. Chai, and S. T. Shou. 2015. The role of regulatory T cells in immune dysfunction during sepsis. World J. Emerg. Med. 6: 5-9.
35. Zelenay, S., T. Lopes-Carvalho, I. Caramalho, M. F. Moraes-Fontes, M. Rebelo, and J. Demengeot. 2005. Foxp3+ CD252 CD4 T cells constitute a reservoir of committed regulatory cells that regain CD25 expression upon homeostatic expansion. Proc. Natl. Acad. Sci. USA 102: 4091-4096.
36. Chang, K. C., C. A. Burnham, S. M. Compton, D. P. Rasche, R. J. Mazuski, J. S. McDonough, J. Unsinger, A. J. Korman, J. M. Green, and R. S. Hotchkiss. 2013. Blockade of the negative co-stimulatory molecules PD-1 and CTLA-4 improves survival in primary and secondary fungal sepsis. Crit. Care 17: R85.
37. Guignant, C., A. Lepape, X. Huang, H. Kherouf, L. Denis, F. Poitevin, C. Malcus, A. Chéron, B. Allaouchiche, F. Gueyffier, et al. 2011. Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients. Crit. Care 15: R99.
38. Arens, C., S. A. Bajwa, C. Koch, B. H. Siegler, E. Schneck, A. Hecker, S.Weiterer, C. Lichtenstern, M. A.Weigand, and F. Uhle. 2016. Sepsis-induced longterm immune paralysis-results of a descriptive, explorative study. Crit. Care 20: 93.
39. Hutchinson, P., L. A. Divola, and S. R. Holdsworth. 1999. Mitogen-induced T-cell CD69 expression is a less sensitive measure of T-cell function than [(3) H]-thymidine uptake. Cytometry 38: 244-249.
40. Reddy, M., E. Eirikis, C. Davis, H. M. Davis, and U. Prabhakar. 2004. Comparative analysis of lymphocyte activation marker expression and cytokine secretion profile in stimulated human peripheral blood mononuclear cell cultures: an in vitro model to monitor cellular immune function. J. Immunol. Methods 293: 127-142.
41. Borges, O., G. Borchard, A. de Sousa, H. E. Junginger, and A. Cordeiro-da-Silva. 2007. Induction of lymphocytes activated marker CD69 following exposure to chitosan and alginate biopolymers. Int. J. Pharm. 337: 254-264.
42. Moran, A. E., K. L. Holzapfel, Y. Xing, N. R. Cunningham, J. S. Maltzman, J. Punt, and K. A. Hogquist. 2011. T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse. J. Exp. Med. 208: 1279-1289.
43. Castle, B. E., K. Kishimoto, C. Stearns, M. L. Brown, and M. R. Kehry. 1993. Regulation of expression of the ligand for CD40 on T helper lymphocytes. J. Immunol. 151: 1777-1788.
44. Jaiswal, A. I., C. Dubey, S. L. Swain, and M. Croft. 1996. Regulation of CD40 ligand expression on naive CD4 T cells: a role for TCR but not co-stimulatory signals. Int. Immunol. 8: 275-285.
45. Arndt, B., M. Poltorak, B. S. Kowtharapu, P. Reichardt, L. Philipsen, J. A. Lindquist, B. Schraven, and L. Simeoni. 2013. Analysis of TCR activation kinetics in primary human T cells upon focal or soluble stimulation. J. Immunol. Methods 387: 276-283.
46. Wang, X., L. Simeoni, J. A. Lindquist, J. Saez-Rodriguez, A. Ambach, E. D. Gilles, S. Kliche, and B. Schraven. 2008. Dynamics of proximal signaling events after TCR/CD8-mediated induction of proliferation or apoptosis in mature CD8+ T cells. J. Immunol. 180: 6703-6712.
47. Berg, N. N., L. G. Puente, W. Dawicki, and H. L. Ostergaard. 1998. Sustained TCR signaling is required for mitogen-activated protein kinase activation and degranulation by cytotoxic T lymphocytes. J. Immunol. 161: 2919-2924.
48. Cantrell, D. A., and K. A. Smith. 1983. Transient expression of interleukin 2 receptors. Consequences for T cell growth. J. Exp. Med. 158: 1895-1911.
49. Cantrell, D. A., and K. A. Smith. 1984. The interleukin-2 T-cell system: a new cell growth model. Science 224: 1312-1316.
50. Unsinger, J., J. M. Herndon, C. G. Davis, J. T. Muenzer, R. S. Hotchkiss, and T. A. Ferguson. 2006. The role of TCR engagement and activation-induced cell death in sepsis-induced T cell apoptosis. J. Immunol. 177: 7968-7973.
51. Venet, F., C. S. Chung, H. Kherouf, A. Geeraert, C. Malcus, F. Poitevin, J. Bohe, A. Lepape, A. Ayala, and G. Monneret. 2009. Increased circulating regulatory T cells (CD4(+)CD25(+)CD127(2)) contribute to lymphocyte anergy in septic shock patients. Intensive Care Med. 35: 678-686.
52. Hotchkiss, R. S., K. W. Tinsley, P. E. Swanson, R. E. Schmieg, Jr., J. J. Hui, K. C. Chang, D. F. Osborne, B. D. Freeman, J. P. Cobb, T. G. Buchman, and I. E. Karl. 2001. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J. Immunol. 166: 6952-6963.
53. Hotchkiss, R. S., S. B. Osmon, K. C. Chang, T. H. Wagner, C. M. Coopersmith, and I. E. Karl. 2005. Accelerated lymphocyte death in sepsis occurs by both the death receptor and mitochondrial pathways. J. Immunol. 174: 5110-5118.
54. Le Tulzo, Y., C. Pangault, A. Gacouin, V. Guilloux, O. Tribut, L. Amiot, P. Tattevin, R. Thomas, R. Fauchet, and B. Drenou. 2002. Early circulating lymphocyte apoptosis in human septic shock is associated with poor outcome. Shock 18: 487-494.
55. Chung, K. P., H. T. Chang, S. C. Lo, L. Y. Chang, S. Y. Lin, A. Cheng, Y. T. Huang, C. C. Chen, M. R. Lee, Y. J. Chen, et al. 2015. Severe lymphopenia is associated with elevated plasma interleukin-15 levels and increased mortality during severe sepsis. Shock 43: 569-575.
56. Boomer, J. S., J. Shuherk-Shaffer, R. S. Hotchkiss, and J. M. Green. 2012. A prospective analysis of lymphocyte phenotype and function over the course of acute sepsis. Crit. Care 16: R112.
57. McAleer, J. P., and A. T. Vella. 2008. Understanding how lipopolysaccharide impacts CD4 T-cell immunity. Crit. Rev. Immunol. 28: 281-299.
58. Brooke, M. S. 1965. Conversion of immunological paralysis to immunity by endotoxin. Nature 206: 635-636.
59. Ben-Sasson, S. Z., S. Caucheteux, M. Crank, J. Hu-Li, and W. E. Paul. 2011. IL-1 acts on T cells to enhance the magnitude of in vivo immune responses. Cytokine 56: 122-125.
60. Ben-Sasson, S. Z., J. Hu-Li, J. Quiel, S. Cauchetaux, M. Ratner, I. Shapira, C. A. Dinarello, and W. E. Paul. 2009. IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation. Proc. Natl. Acad. Sci. USA 106: 7119-7124.
61. Liu, W., A. Menoret, and A. T. Vella. 2017. Responses to LPS boost effector CD8 T-cell accumulation outside of signals 1 and 2. Cell. Mol. Immunol. 14: 254-253.
62. Hahn, P. Y., P. Wang, S. M. Tait, Z. F. Ba, S. S. Reich, and I. H. Chaudry. 1995. Sustained elevation in circulating catecholamine levels during polymicrobial sepsis. Shock 4: 269-273.
63. Wang, P., S. M. Tait, and I. H. Chaudry. 2000. Sustained elevation of norepinephrine depresses hepatocellular function. Biochim. Biophys. Acta 1535: 36-44.
64. Gogos, C. A., E. Drosou, H. P. Bassaris, and A. Skoutelis. 2000. Pro- versus antiinflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J. Infect. Dis. 181: 176-180.
65. Steinhauser, M. L., C. M. Hogaboam, S. L. Kunkel, N.W. Lukacs, R. M. Strieter, and T. J. Standiford. 1999. IL-10 is a major mediator of sepsis-induced impairment in lung antibacterial host defense. J. Immunol. 162: 392-399.
66. Strell, C., A. Sievers, P. Bastian, K. Lang, B. Niggemann, K. S. Zanker, and F. Entschladen. 2009. Divergent effects of norepinephrine, dopamine and substance P on the activation, differentiation and effector functions of human cytotoxic T lymphocytes. BMC Immunol. 10: 62.
67. Bejarano, M. T., R. de Waal Malefyt, J. S. Abrams, M. Bigler, R. Bacchetta, J. E. de Vries, and M. G. Roncarolo. 1992. Interleukin 10 inhibits allogeneic proliferative and cytotoxic T cell responses generated in primary mixed lymphocyte cultures. Int. Immunol. 4: 1389-1397.
68. van Vught, L. A., P.M. Klein Klouwenberg, C. Spitoni, B. P. Scicluna, M. A.Wiewel, J. Horn, M. J. Schultz, P. Nurnberg, M. J. Bonten, O. L. Cremer, and T. van der Poll. 2016. Incidence, risk factors, and attributable mortality of secondary infections in the intensive care unit after admission for sepsis. JAMA 315: 1469-1479.
69. Monneret, G., M. E. Finck, F. Venet, A. L. Debard, J. Bohe, J. Bienvenu, and A. Lepape. 2004. The anti-inflammatory response dominates after septic shock: association of low monocyte HLA-DR expression and high interleukin-10 concentration. Immunol. Lett. 95: 193-198.
70. Cajander, S., A. Backman, E. Tina, K. Stralin, B. Soderquist, and J. Kallman. 2013. Preliminary results in quantitation of HLA-DRA by real-time PCR: a promising approach to identify immunosuppression in sepsis. Crit. Care 17: R223.
71. Docke, W. D., C. Hoflich, K. A. Davis, K. Rottgers, C. Meisel, P. Kiefer, S. U. Weber, M. Hedwig-Geissing, E. Kreuzfelder, P. Tschentscher, et al. 2005. Monitoring temporary immunodepression by flow cytometric measurement of monocytic HLA-DR expression: a multicenter standardized study. Clin. Chem. 51: 2341-2347.
72. Döcke, W. D., F. Randow, U. Syrbe, D. Krausch, K. Asadullah, P. Reinke, H. D. Volk, and W. Kox. 1997. Monocyte deactivation in septic patients: restoration by IFN-gamma treatment. Nat. Med. 3: 678-681.
73. Unsinger, J., M. McGlynn, K. R. Kasten, A. S. Hoekzema, E. Watanabe, J. T. Muenzer, J. S. McDonough, J. Tschoep, T. A. Ferguson, J. E. McDunn, et al. 2010. IL-7 promotes T cell viability, trafficking, and functionality and improves survival in sepsis. J. Immunol. 184: 3768-3779.