Adoptive Transfer of EBV Specific CD8 T Cell Clones Can Transiently Control EBV Infection in Humanized Mice

English version České info

Epstein Barr virus persistently infects more than 90% of the human adult population. While fortunately carried as an asymptomatic chronic infection in most individuals, it causes B cell lymphomas and carcinomas in some patients. Symptomatic primary EBV infection, called infectious mononucleosis, predisposes for some of these malignancies and is characterized by massive expansions of cytotoxic T cells, which are mostly directed against lytic EBV antigens that are expressed during virus particle production. Therefore, we investigated the protective role of lytic EBV antigen specific T cells during EBV infection and the contribution of lytic EBV infection to virus-associated tumor formation. We found that lytic EBV antigen specific T cells kill B cells with lytic virus replication and might thereby transiently control EBV infection in mice with human immune system components. Furthermore, we observed that EBV associated B cell tumors outside secondary lymphoid organs may require lytic replication for efficient formation. Thus, we suggest that lytic EBV antigens should be explored for vaccination against symptomatic EBV infection and EBV associated extra-lymphoid tumors.

Vyšlo v časopise: Adoptive Transfer of EBV Specific CD8 T Cell Clones Can Transiently Control EBV Infection in Humanized Mice. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004333
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004333

Souhrn

Zdroje

1. YoungLS, RickinsonAB (2004) Epstein-Barr virus: 40 years on. Nat Rev Cancer 4 : 757–768.

2. KutokJL, WangF (2006) Spectrum of Epstein-Barr virus-associated diseases. Annu Rev Pathol 1 : 375–404.

3. MillerG, El-GuindyA, CountrymanJ, YeJ, GradovilleL (2007) Lytic cycle switches of oncogenic human gammaherpesviruses. Adv Cancer Res 97 : 81–109.

4. HislopAD, TaylorGS, SauceD, RickinsonAB (2007) Cellular responses to viral infection in humans: lessons from epstein-barr virus. Annu Rev Immunol 25 : 587–617.

5. MünzC, BickhamKL, SubkleweM, TsangML, ChahroudiA, et al. (2000) Human CD4+ T lymphocytes consistently respond to the latent Epstein-Barr virus nuclear antigen EBNA1. J Exp Med 191 : 1649–1660.

6. MurrayRJ, KurillaMG, BrooksJM, ThomasWA, RoweM, et al. (1992) Identification of target antigens for the human cytotoxic T cell response to Epstein-Barr virus (EBV): implications for the immune control of EBV-positive malignancies. J Exp Med 176 : 157–168.

7. AdhikaryD, BehrendsU, MoosmannA, WitterK, BornkammGW, et al. (2006) Control of Epstein-Barr virus infection in vitro by T helper cells specific for virion glycoproteins. J Exp Med 203 : 995–1006.

8. StevenNM, AnnelsNE, KumarA, LeeseAM, KurillaMG, et al. (1997) Immediate early and early lytic cycle proteins are frequent targets of the Epstein-Barr virus-induced cytotoxic T cell response. J Exp Med 185 : 1605–1617.

9. ChoYG, GordadzeAV, LingPD, WangF (1999) Evolution of two types of rhesus lymphocryptovirus similar to type 1 and type 2 Epstein-Barr virus. J Virol 73 : 9206–9212.

10. LeungC, ChijiokeO, GujerC, ChatterjeeB, AntsiferovaO, et al. (2013) Infectious diseases in humanized mice. Eur J Immunol 43 : 2246–2254.

11. OhashiM, FoggMH, OrlovaN, QuinkC, WangF (2012) An Epstein-Barr virus encoded inhibitor of Colony Stimulating Factor-1 signaling is an important determinant for acute and persistent EBV infection. PLoS Pathog 8: e1003095.

12. Marr-BelvinAK, CarvilleAK, FaheyMA, BoisvertK, KlumppSA, et al. (2008) Rhesus lymphocryptovirus type 1-associated B-cell nasal lymphoma in SIV-infected rhesus macaques. Vet Pathol 45 : 914–921.

13. StrowigT, GurerC, PlossA, LiuYF, ArreyF, et al. (2009) Priming of protective T cell responses against virus-induced tumors in mice with human immune system components. J Exp Med 206 : 1423–1434.

14. ChijiokeO, MüllerA, FeederleR, BarrosMH, KriegC, et al. (2013) Natural killer cells prevent infectious mononucleosis features by targeting lytic Epstein-Barr virus infection. Cell Rep 5 : 1489–1498.

15. StrowigT, ChijiokeO, CarregaP, ArreyF, MeixlspergerS, et al. (2010) Human NK cells of mice with reconstituted human immune system components require preactivation to acquire functional competence. Blood 116 : 4158–4167.

16. GurerC, StrowigT, BrilotF, PackM, TrumpfhellerC, et al. (2008) Targeting the nuclear antigen 1 of Epstein Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses. Blood 112 : 1231–1239.

17. MeixlspergerS, LeungCS, RamerPC, PackM, VanoaicaLD, et al. (2013) CD141+ dendritic cells produce prominent amounts of IFN-alpha after dsRNA recognition and can be targeted via DEC-205 in humanized mice. Blood 121 : 5034–5044.

18. WhiteRE, RamerPC, NareshKN, MeixlspergerS, PinaudL, et al. (2012) EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is found in human tumors. J Clin Invest 122 : 1487–1502.

19. TsaiMH, RaykovaA, KlinkeO, BernhardtK, GartnerK, et al. (2013) Spontaneous Lytic Replication and Epitheliotropism Define an Epstein-Barr Virus Strain Found in Carcinomas. Cell Rep 5 : 458–70.

20. BergerC, DayP, MeierG, ZinggW, BossartW, et al. (2001) Dynamics of Epstein-Barr virus DNA levels in serum during EBV-associated disease. J Med Virol 64 : 505–512.

21. FonteneauJF, LarssonM, SomersanS, SandersC, MünzC, et al. (2001) Generation of high quantities of viral and tumor-specific human CD4+ and CD8+ T-cell clones using peptide pulsed mature dendritic cells. J Immunol Methods 258 : 111–126.

22. YousefS, PlanasR, ChakrounK, Hoffmeister-UllerichS, BinderTM, et al. (2012) TCR bias and HLA cross-restriction are strategies of human brain-infiltrating JC virus-specific CD4+ T cells during viral infection. J Immunol 189 : 3618–3630.

23. RessingME, KeatingSE, van LeeuwenD, Koppers-LalicD, PappworthIY, et al. (2005) Impaired transporter associated with antigen processing-dependent peptide transport during productive EBV infection. J Immunol 174 : 6829–6838.

24. FeederleR, KostM, BaumannM, JanzA, DrouetE, et al. (2000) The Epstein-Barr virus lytic program is controlled by the co-operative functions of two transactivators. Embo J 19 : 3080–3089.

25. KatsumuraKR, MaruoS, WuY, KandaT, TakadaK (2009) Quantitative evaluation of the role of Epstein-Barr virus immediate-early protein BZLF1 in B-cell transformation. J Gen Virol 90 : 2331–2341.

26. HongGK, GulleyML, FengWH, DelecluseHJ, Holley-GuthrieE, et al. (2005) Epstein-Barr virus lytic infection contributes to lymphoproliferative disease in a SCID mouse model. J Virol 79 : 13993–14003.

27. ShultzLD, SaitoY, NajimaY, TanakaS, OchiT, et al. (2010) Generation of functional human T-cell subsets with HLA-restricted immune responses in HLA class I expressing NOD/SCID/IL2r gammanull humanized mice. Proc Natl Acad Sci U S A 107 : 13022–13027.

28. MaSD, HegdeS, YoungKH, SullivanR, RajeshD, et al. (2011) A new model of Epstein-Barr virus infection reveals an important role for early lytic viral protein expression in the development of lymphomas. J Virol 85 : 165–177.

29. MelenhorstJJ, LeenAM, BollardCM, QuigleyMF, PriceDA, et al. (2010) Allogeneic virus-specific T cells with HLA alloreactivity do not produce GVHD in human subjects. Blood 116 : 4700–4702.

30. LeenAM, BollardCM, MendizabalAM, ShpallEJ, SzabolcsP, et al. (2013) Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood 121 : 5113–5123.

31. LuzuriagaK, SullivanJL (2010) Infectious mononucleosis. N Engl J Med 362 : 1993–2000.

32. CallanMF, TanL, AnnelsN, OggGS, WilsonJD, 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.

33. AbbottRJ, QuinnLL, LeeseAM, ScholesHM, PachnioA, et al. (2013) CD8+ T cell responses to lytic EBV infection: late antigen specificities as subdominant components of the total response. J Immunol 191 : 5398–5409.

34. PudneyVA, LeeseAM, RickinsonAB, HislopAD (2005) CD8+ immunodominance among Epstein-Barr virus lytic cycle antigens directly reflects the efficiency of antigen presentation in lytically infected cells. J Exp Med 201 : 349–360.

35. RooneyCM, SmithCA, NgCY, LoftinS, LiC, et al. (1995) Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet 345 : 9–13.

36. AdhikaryD, BehrendsU, BoerschmannH, PfunderA, BurdachS, et al. (2007) Immunodominance of lytic cycle antigens in Epstein-Barr virus-specific CD4+ T cell preparations for therapy. PLoS ONE 2: e583.

37. HaqueT, WilkieGM, TaylorC, AmlotPL, MuradP, et al. (2002) Treatment of Epstein-Barr-virus-positive post-transplantation lymphoproliferative disease with partly HLA-matched allogeneic cytotoxic T cells. Lancet 360 : 436–442.

38. HaqueT, WilkieGM, JonesMM, HigginsCD, UrquhartG, et al. (2007) Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial. Blood 110 : 1123–1131.

39. DoubrovinaE, Oflaz-SozmenB, ProckopSE, KernanNA, AbramsonS, et al. (2012) Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation. Blood 119 : 2644–2656.

40. BoltonDL, MinangJT, TrivettMT, SongK, TuscherJJ, et al. (2010) Trafficking, persistence, and activation state of adoptively transferred allogeneic and autologous Simian Immunodeficiency Virus-specific CD8+ T cell clones during acute and chronic infection of rhesus macaques. J Immunol 184 : 303–314.

41. SokalEM, HoppenbrouwersK, VandermeulenC, MoutschenM, LeonardP, et al. (2007) Recombinant gp350 vaccine for infectious mononucleosis: a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virus vaccine in healthy young adults. J Infect Dis 196 : 1749–1753.

42. CuiX, CaoZ, SenG, ChattopadhyayG, FullerDH, et al. (2013) A novel tetrameric gp350 1–470 as a potential Epstein-Barr virus vaccine. Vaccine 31 : 3039–3045.

43. OgemboJG, KannanL, GhiranI, Nicholson-WellerA, FinbergRW, et al. (2013) Human complement receptor type 1/CD35 is an Epstein-Barr Virus receptor. Cell Rep 3 : 371–385.

44. HuiEP, TaylorGS, JiaH, MaBB, ChanSL, et al. (2013) Phase I trial of recombinant modified vaccinia ankara encoding Epstein-Barr viral tumor antigens in nasopharyngeal carcinoma patients. Cancer Res 73 : 1676–1688.

45. TaylorGS, HaighTA, GudgeonNH, PhelpsRJ, LeeSP, et al. (2004) Dual stimulation of Epstein-Barr Virus (EBV)-specific CD4+ -⁠ and CD8+-T-cell responses by a chimeric antigen construct: potential therapeutic vaccine for EBV-positive nasopharyngeal carcinoma. J Virol 78 : 768–778.

46. RuissR, JochumS, WannerG, ReisbachG, HammerschmidtW, et al. (2011) A virus-like particle-based Epstein-Barr virus vaccine. J Virol 85 : 13105–13113.

47. FeederleR, Shannon-LoweC, BaldwinG, DelecluseHJ (2005) Defective infectious particles and rare packaged genomes produced by cells carrying terminal-repeat-negative Epstein-Barr virus. J Virol 79 : 7641–7647.

48. AdhikaryD, BehrendsU, FeederleR, DelecluseHJ, MautnerJ (2008) Standardized and highly efficient expansion of Epstein-Barr virus-specific CD4+ T cells by using virus-like particles. J Virol 82 : 3903–3911.

49. PavlovaS, FeederleR, GartnerK, FuchsW, GranzowH, et al. (2013) An Epstein-Barr virus mutant produces immunogenic defective particles devoid of viral DNA. J Virol 87 : 2011–2022.

50. LeungCS, MaurerMA, MeixlspergerS, LippmannA, CheongC, et al. (2013) Robust T cell stimulation by Epstein-Barr virus-transformed B cells after antigen targeting to DEC-205. Blood 121 : 1584–94.