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Specificity and Dynamics of Effector and Memory CD8 T Cell Responses in Human Tick-Borne Encephalitis Virus Infection


Tick-borne encephalitis virus (TBEV) belongs to the flavivirus family and causes tick-borne encephalitis. This is a severe meningoencephalitic disease with no available treatment. Detailed studies of the immune response during human TBEV infection are essential to understand host responses to TBE and for the development of therapeutics. Herein, we studied the primary T cell-mediated immune response in patients diagnosed with TBEV infection. We show that CD8 T cells mount a vigorous TBEV-specific response within one week of hospitalization. Moreover, TBEV-specific CD8 T cells displayed a distinctive phenotypic and functional profile, paired with a distinct transcription factor expression-pattern during the peak of activation. In summary, this is the first comprehensive study of the CD8 T cell response during acute human TBEV infection, and provides a framework for understanding of CD8 T cell-mediated immunity in this emerging viral disease.


Vyšlo v časopise: Specificity and Dynamics of Effector and Memory CD8 T Cell Responses in Human Tick-Borne Encephalitis Virus Infection. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004622
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004622

Souhrn

Tick-borne encephalitis virus (TBEV) belongs to the flavivirus family and causes tick-borne encephalitis. This is a severe meningoencephalitic disease with no available treatment. Detailed studies of the immune response during human TBEV infection are essential to understand host responses to TBE and for the development of therapeutics. Herein, we studied the primary T cell-mediated immune response in patients diagnosed with TBEV infection. We show that CD8 T cells mount a vigorous TBEV-specific response within one week of hospitalization. Moreover, TBEV-specific CD8 T cells displayed a distinctive phenotypic and functional profile, paired with a distinct transcription factor expression-pattern during the peak of activation. In summary, this is the first comprehensive study of the CD8 T cell response during acute human TBEV infection, and provides a framework for understanding of CD8 T cell-mediated immunity in this emerging viral disease.


Zdroje

1. Gritsun TS, Nuttall PA, Gould EA (2003) Tick-borne flaviviruses. Adv Virus Res 61: 317–371. doi: 10.1016/S0065-3527(03)61008-0 14714436

2. Lindquist L, Vapalahti O (2008) Tick-borne encephalitis. Lancet 371: 1861–1871. doi: 10.1016/S0140-6736(08)60800-4 18514730

3. Gustafson R, Svenungsson B, Forsgren M, Gardulf A, Granström M (1992) Two-year survey of the incidence of Lyme borreliosis and tick-borne encephalitis in a high-risk population in Sweden. Eur J Clin Microbiol Infect Dis 11: 894–900. doi: 10.1007/BF01962369 1486884

4. Gustafson R, Svenungsson B, Gardulf A, Stiernstedt G, Forsgren M (1990) Prevalence of tick-borne encephalitis and Lyme borreliosis in a defined Swedish population. Scand J Infect Dis 22: 297–306. doi: 10.3109/00365549009027051 2371545

5. Haglund M, Günther G (2003) Tick-borne encephalitis--pathogenesis, clinical course and long-term follow-up. Vaccine 21 Suppl 1: S11–S18. doi: 10.1016/S0264-410X(02)00811-3 12628810

6. Gelpi E, Preusser M, Garzuly F, Holzmann H, Heinz FX, et al. (2005) Visualization of Central European tick-borne encephalitis infection in fatal human cases. J Neuropathol Exp Neurol 64: 506–512. 15977642

7. Günther G, Haglund M, Lindquist L, Sköldenberg B, Forsgren M (1997) Intrathecal IgM, IgA and IgG antibody response in tick-borne encephalitis. Long-term follow-up related to clinical course and outcome. Clin Diagn Virol 8: 17–29.

8. Gelpi E, Preusser M, Laggner U, Garzuly F, Holzmann H, et al. (2006) Inflammatory response in human tick-borne encephalitis: analysis of postmortem brain tissue. J Neurovirol 12: 322–327. doi: 10.1080/13550280600848746 16966222

9. Růžek D, Salát J, Palus M, Gritsun TS, Gould EA, et al. (2009) CD8+ T-cells mediate immunopathology in tick-borne encephalitis. Virology 384: 1–6. doi: 10.1016/j.virol.2008.11.023 19070884

10. Fujii Y, Hayasaka D, Kitaura K, Takasaki T, Suzuki R, et al. (2011) T-cell clones expressing different T-cell receptors accumulate in the brains of dying and surviving mice after peripheral infection with far eastern strain of tick-borne encephalitis virus. Viral Immunol 24: 291–302. doi: 10.1089/vim.2011.0017 21830901

11. Butz EA, Bevan MJ (1998) Massive expansion of antigen-specific CD8+ T cells during an acute virus infection. Immunity 8: 167–175. doi: 10.1016/S1074-7613(00)80469-0 9491998

12. Harrington LE, Most Rv RVD, Whitton JL, Ahmed R (2002) Recombinant vaccinia virus-induced T-cell immunity: quantitation of the response to the virus vector and the foreign epitope. J Virol 76: 3329–3337. doi: 10.1128/JVI.76.7.3329-3337.2002 11884558

13. Murali-Krishna K, Altman JD, Suresh M, Sourdive DJ, Zajac AJ, et al. (1998) Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity 8: 177–187. doi: 10.1016/S1074-7613(00)80470-7 9491999

14. Appay V, Douek DC, Price DA (2008) CD8+ T cell efficacy in vaccination and disease. Nat Med 14: 623–628. doi: 10.1038/nm.f.1774 18535580

15. Callan MF, Tan L, Annels N, Ogg GS, Wilson JD, et al. (1998) Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein-Barr virus In vivo. J Exp Med 187: 1395–1402. doi: 10.1084/jem.187.9.1395 9565632

16. Roos MT, van Lier RA, Hamann D, Knol GJ, Verhoofstad I, et al. (2000) Changes in the composition of circulating CD8+ T cell subsets during acute epstein-barr and human immunodeficiency virus infections in humans. J Infect Dis 182: 451–458. doi: 10.1086/315737 10915075

17. Appay V, Rowland-Jones SL (2004) Lessons from the study of T-cell differentiation in persistent human virus infection. Seminars in Immunology 16: 205–212. doi: 10.1016/j.smim.2004.02.007 15130505

18. Sallusto F, Lenig D, Förster R, Lipp M, Lanzavecchia A (1999) Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401: 708–712. doi: 10.1038/44385 10537110

19. Champagne P, Ogg GS, King AS, Knabenhans C, Ellefsen K, et al. (2001) Skewed maturation of memory HIV-specific CD8 T lymphocytes. Nature 410: 106–111. doi: 10.1038/35065118 11242051

20. Akondy RS, Monson ND, Miller JD, Edupuganti S, Teuwen D, et al. (2009) The Yellow Fever Virus Vaccine Induces a Broad and Polyfunctional Human Memory CD8+ T Cell Response. J Immunol 183: 7919–7930. doi: 10.4049/jimmunol.0803903 19933869

21. Blom K, Braun M, Ivarsson MA, Gonzalez VD, Falconer K, et al. (2013) Temporal dynamics of the primary human T cell response to yellow fever virus 17D as it matures from an effector- to a memory-type response. J Immunol 190: 2150–2158. doi: 10.4049/jimmunol.1202234 23338234

22. Miller JD, van der Most RG, Akondy RS, Glidewell JT, Albott S, et al. (2008) Human Effector and Memory CD8+ T Cell Responses to Smallpox and Yellow Fever Vaccines. Immunity 28: 710–722. doi: 10.1016/j.immuni.2008.02.020 18468462

23. Joshi NS, Cui W, Chandele A, Lee HK, Urso DR, et al. (2007) Inflammation Directs Memory Precursor and Short-Lived Effector CD8+ T Cell Fates via the Graded Expression of T-bet Transcription Factor. Immunity 27: 281–295. doi: 10.1016/j.immuni.2007.07.010 17723218

24. Intlekofer AM, Takemoto N, Wherry EJ, Longworth SA, Northrup JT, et al. (2005) Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. Nat Immunol 6: 1236–1244. doi: 10.1038/ni1268 16273099

25. Kao C, Oestreich KJ, Paley MA, Crawford A, Angelosanto JM, et al. (2011) Transcription factor T-bet represses expression of the inhibitory receptor PD-1 and sustains virus-specific CD8+ T cell responses during chronic infection. Nat Immunol 12: 663–671. doi: 10.1038/ni.2046 21623380

26. Paley MA, Kroy DC, Odorizzi PM, Johnnidis JB, Dolfi DV, et al. (2012) Progenitor and terminal subsets of CD8+ T cells cooperate to contain chronic viral infection. Science 338: 1220–1225. doi: 10.1126/science.1229620 23197535

27. Mickiene A, Laiskonis A, Günther G, Vene S, Lundkvist A, et al. (2002) Tickborne encephalitis in an area of high endemicity in lithuania: disease severity and long-term prognosis. Clin Infect Dis 35: 650–658. doi: 10.1086/342059 12203160

28. Appay V, Dunbar PR, Callan M, Klenerman P, Gillespie GMA, et al. (2002) Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat Med 8: 379–385. doi: 10.1038/nm0402-379 11927944

29. Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, et al. (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133: 1710–1715. 6206131

30. Sarkar S, Kalia V, Haining WN, Konieczny BT, Subramaniam S, et al. (2008) Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates. Journal of Experimental Medicine 205: 625–640. doi: 10.1084/jem.20071641 18316415

31. Rutishauser RL, Kaech SM (2010) Generating diversity: transcriptional regulation of effector and memory CD8 T-cell differentiation. Immunol Rev 235: 219–233. 20536566

32. Akimova T, Beier UH, Wang L, Levine MH, Hancock WW (2011) Helios expression is a marker of T cell activation and proliferation. PLoS ONE 6: e24226. doi: 10.1371/journal.pone.0024226 21918685

33. van Aalderen MC, Remmerswaal EBM, Heutinck KM, Brinke Ten A, Pircher H, et al. (2013) Phenotypic and functional characterization of circulating polyomavirus BK VP1-specific CD8+ T cells in healthy adults. J Virol 87(18): 10263–10272. doi: 10.1128/JVI.01540-13 23864628

34. Pearce EL, Mullen AC, Martins GA, Krawczyk CM, Hutchins AS, et al. (2003) Control of effector CD8+ T cell function by the transcription factor Eomesodermin. Science 302: 1041–1043. doi: 10.1126/science.1090148 14605368

35. Banerjee A, Gordon SM, Intlekofer AM, Paley MA, Mooney EC, et al. (2010) Cutting edge: The transcription factor eomesodermin enables CD8+ T cells to compete for the memory cell niche. J Immunol 185: 4988–4992. doi: 10.4049/jimmunol.1002042 20935204

36. Pipkin ME, Sacks JA, Cruz-Guilloty F, Lichtenheld MG, Bevan MJ, et al. (2010) Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells. Immunity 32: 79–90. doi: 10.1016/j.immuni.2009.11.012 20096607

37. Intlekofer AM, Takemoto N, Kao C, Banerjee A, Schambach F, et al. (2007) Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T cells. J Exp Med 204: 2015–2021. doi: 10.1084/jem.20070841 17698591

38. Joshi NS, Cui W, Dominguez CX, Chen JH, Hand TW, et al. (2011) Increased numbers of preexisting memory CD8 T cells and decreased T-bet expression can restrain terminal differentiation of secondary effector and memory CD8 T cells. J Immunol 187: 4068–4076. doi: 10.4049/jimmunol.1002145 21930973

39. Wang JH, Nichogiannopoulou A, Wu L, Sun L, Sharpe AH, et al. (1996) Selective defects in the development of the fetal and adult lymphoid system in mice with an Ikaros null mutation. Immunity 5: 537–549. doi: 10.1016/S1074-7613(00)80269-1 8986714

40. Urban JA, Winandy S (2004) Ikaros null mice display defects in T cell selection and CD4 versus CD8 lineage decisions. J Immunol 173: 4470–4478. doi: 10.4049/jimmunol.173.7.4470 15383578

41. Makedonas G, Hutnick N, Haney D, Amick AC, Gardner J, et al. (2010) Perforin and IL-2 upregulation define qualitative differences among highly functional virus-specific human CD8 T cells. PLoS Pathog 6: e1000798. doi: 10.1371/journal.ppat.1000798 20221423

42. Puchhammer-Stöckl E, Kunz C, Mandl CW, Heinz FX (1995) Identification of tick-borne encephalitis virus ribonucleic acid in tick suspensions and in clinical specimens by a reverse transcription-nested polymerase chain reaction assay. Clin Diagn Virol 4: 321–326. doi: 10.1016/0928-0197(95)00022-4 15566853

43. Saksida A, Duh D, Lotric-Furlan S, Strle F, Petrovec M, et al. (2005) The importance of tick-borne encephalitis virus RNA detection for early differential diagnosis of tick-borne encephalitis. J of Clin Virol 33: 331–335. doi: 10.1016/j.jcv.2004.07.014

44. Tomazic J, Poljak M, Popovic P, Maticic M, Beovic B, et al. (1997) Tick-borne encephalitis: possibly a fatal disease in its acute stage. PCR amplification of TBE RNA from postmortem brain tissue. Infection 25: 41–43.

45. Mizuno Y, Kotaki A, Harada F, Tajima S, Kurane I, et al. (2007) Confirmation of dengue virus infection by detection of dengue virus type 1 genome in urine and saliva but not in plasma. Trans R Soc Trop Med Hyg 101: 738–739. doi: 10.1016/j.trstmh.2007.02.007 17418320

46. Domingo C, Yactayo S, Agbenu E, Demanou M, Schulz AR, et al. (2011) Detection of yellow fever 17D genome in urine. J Clin Microbiol 49: 760–762. doi: 10.1128/JCM.01775-10 21106799

47. Barzon L, Pacenti M, Franchin E, Pagni S, Martello T, et al. (2013) Excretion of West Nile virus in urine during acute infection. J Infect Dis 208: 1086–1092. doi: 10.1093/infdis/jit290 23821721

48. Lindgren T, Ahlm C, Mohamed N, Evander M, Ljunggren H-G, et al. (2011) Longitudinal analysis of the human T cell response during acute hantavirus infection. J Virol 85: 10252–10260. doi: 10.1128/JVI.05548-11 21795350

49. Hess C, Altfeld M, Thomas SY, Addo MM, Rosenberg ES, et al. (2004) HIV-1 specific CD8+ T cells with an effector phenotype and control of viral replication. Lancet 363: 863–866. doi: 10.1016/S0140-6736(04)15735-8 15031033

50. Northfield JW, Loo CP, Barbour JD, Spotts G, Hecht FM, et al. (2007) Human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T(EMRA) cells in early infection are linked to control of HIV-1 viremia and predict the subsequent viral load set point. J Virol 81: 5759–5765. doi: 10.1128/JVI.00045-07 17376902

51. Appay V, van Lier RAW, Sallusto F, Roederer M (2008) Phenotype and function of human T lymphocyte subsets: consensus and issues. Cytometry A 73: 975–983. doi: 10.1002/cyto.a.20643 18785267

52. Sandberg JK, Fast NM, Nixon DF (2001) Functional heterogeneity of cytokines and cytolytic effector molecules in human CD8+ T lymphocytes. J Immunol 167: 181–187. doi: 10.4049/jimmunol.167.1.181 11418647

53. Newell EW, Sigal N, Bendall SC, Nolan GP, Davis MM (2012) Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes. Immunity 36: 142–152. doi: 10.1016/j.immuni.2012.01.002 22265676

54. Andersson CR, Vene S, Insulander M, Lindquist L, Lundkvist A, et al. (2010) Vaccine failures after active immunisation against tick-borne encephalitis. Vaccine 28: 2827–2831. doi: 10.1016/j.vaccine.2010.02.001 20167301

55. Roederer M, Nozzi JL, Nason MX (2011) SPICE: Exploration and analysis of post-cytometric complex multivariate datasets. Cytometry A. 79A(2): 167–174. doi: 10.1002/cyto.a.21015

56. Larsen MV, Lundegaard C, Lamberth K, Buus S, Lund O, et al. (2007) Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction. BMC Bioinformatics 8: 424. doi: 10.1186/1471-2105-8-424 17973982

57. Schwaiger M, Cassinotti P (2003) Development of a quantitative real-time RT-PCR assay with internal control for the laboratory detection of tick borne encephalitis virus (TBEV) RNA. J Clin Virol 27: 136–145. doi: 10.1016/S1386-6532(02)00168-3 12829035

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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