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Conference Paper: Development of Immunodominance Hierarchies Concurrent with Enhanced Polyfunctionality in T Cell Immunity Towards Epstein-Barr Virus

TitleDevelopment of Immunodominance Hierarchies Concurrent with Enhanced Polyfunctionality in T Cell Immunity Towards Epstein-Barr Virus
Authors
Issue Date2013
PublisherMedcom Limited. The Journal's web site is located at http://www.hkjpaed.org/index.asp
Citation
Joint Annual Scientific Meeting 2013 of The Hong Kong Paediatric Society and Hong Kong Paediatric Nurses Association, Hong Kong, 8 September 2013. In Hong Kong Journal of Paediatrics (New series), 2013, v. 18 n. 4, p. 253 How to Cite?
AbstractBackground: EBV-specific T-cell immunity is characterised by immunodominant responses towards certain lytic and latent viral proteins. Nevertheless, how such immunodominance hierarchy develops with T-cell functionality from early stage of primary infection to long term persistency remains unclear. This study aims to study i) the difference in CD4+ and CD8+ EBV-specific T cell functions between early and late stage of viral infection; ii) correlation of immunodominant responses to the functionality of T cells. Methods: PBMCs of ten patients with infectious mononucleosis (IM) and four individuals with asymptomatic EBV primary infection (NIM) were collected longitudinally from the onset of disease through 12-month post infection. Cells were stimulated with overlapping peptides of four lytic-(BZLF1, BRLF1, BMLF1, and GP350) and five latent- (EBNA1, EBNA3A- 3C, and LMP2) proteins, followed by a 9-color flow cytometric assay examining the coexpression of three cytokines (interferon-γ [IFN-γ], tumour necrosis factor- α [TNF-α] and interleukin-2 [IL-2]), perforin and CD107a (degranulation marker) in CD4+ and CD8+ T cells. Stimulated T cells were selected and tested for the cytotoxicity against autologous EBV-transformed lymphoblastoid cell lines (LCLs) and the proliferation capacity. Results: In both IM and NIM individuals there was a gradual shift of CD8+ T cell responses from targeting the BZLF1 or BRLF1 proteins in acute phase to the EBNA3 proteins in persistent phase of infection, and a shift of CD4+ T cell responses from a broad range of early and late lytic proteins to the EBNA-1 protein over time. Such establishment of immunodominance concurred with increased proportion of lytic- and latent-protein specific CD4+ and CD8+ T cells with multiple functions, which presented enhanced proliferation capacity and cytotoxicity against lysing LCLs. Conclusions: T cells simultaneously producing multiple cytokines with effective cytotoxicity and proliferation were generated along with establishment of immunodominance hierarchy in EBV-specific T cells. Formation of effective long-term immunity towards EBV requires both sufficient quantity of latent-specific T cells and highly functional T cells.
DescriptionPoster Presentation (Doctor’s Session)
Fulltext of the abstract in: http://www.hkjpaed.org/pdf/2013;18;230-265.pdf
Persistent Identifierhttp://hdl.handle.net/10722/190075
ISSN
2015 Impact Factor: 0.194
2015 SCImago Journal Rankings: 0.123

 

DC FieldValueLanguage
dc.contributor.authorNing, Jen_US
dc.contributor.authorChan, KHen_US
dc.contributor.authorChiang, AKSen_US
dc.date.accessioned2013-09-17T15:07:19Z-
dc.date.available2013-09-17T15:07:19Z-
dc.date.issued2013en_US
dc.identifier.citationJoint Annual Scientific Meeting 2013 of The Hong Kong Paediatric Society and Hong Kong Paediatric Nurses Association, Hong Kong, 8 September 2013. In Hong Kong Journal of Paediatrics (New series), 2013, v. 18 n. 4, p. 253en_US
dc.identifier.issn1013-9923-
dc.identifier.urihttp://hdl.handle.net/10722/190075-
dc.descriptionPoster Presentation (Doctor’s Session)-
dc.descriptionFulltext of the abstract in: http://www.hkjpaed.org/pdf/2013;18;230-265.pdf-
dc.description.abstractBackground: EBV-specific T-cell immunity is characterised by immunodominant responses towards certain lytic and latent viral proteins. Nevertheless, how such immunodominance hierarchy develops with T-cell functionality from early stage of primary infection to long term persistency remains unclear. This study aims to study i) the difference in CD4+ and CD8+ EBV-specific T cell functions between early and late stage of viral infection; ii) correlation of immunodominant responses to the functionality of T cells. Methods: PBMCs of ten patients with infectious mononucleosis (IM) and four individuals with asymptomatic EBV primary infection (NIM) were collected longitudinally from the onset of disease through 12-month post infection. Cells were stimulated with overlapping peptides of four lytic-(BZLF1, BRLF1, BMLF1, and GP350) and five latent- (EBNA1, EBNA3A- 3C, and LMP2) proteins, followed by a 9-color flow cytometric assay examining the coexpression of three cytokines (interferon-γ [IFN-γ], tumour necrosis factor- α [TNF-α] and interleukin-2 [IL-2]), perforin and CD107a (degranulation marker) in CD4+ and CD8+ T cells. Stimulated T cells were selected and tested for the cytotoxicity against autologous EBV-transformed lymphoblastoid cell lines (LCLs) and the proliferation capacity. Results: In both IM and NIM individuals there was a gradual shift of CD8+ T cell responses from targeting the BZLF1 or BRLF1 proteins in acute phase to the EBNA3 proteins in persistent phase of infection, and a shift of CD4+ T cell responses from a broad range of early and late lytic proteins to the EBNA-1 protein over time. Such establishment of immunodominance concurred with increased proportion of lytic- and latent-protein specific CD4+ and CD8+ T cells with multiple functions, which presented enhanced proliferation capacity and cytotoxicity against lysing LCLs. Conclusions: T cells simultaneously producing multiple cytokines with effective cytotoxicity and proliferation were generated along with establishment of immunodominance hierarchy in EBV-specific T cells. Formation of effective long-term immunity towards EBV requires both sufficient quantity of latent-specific T cells and highly functional T cells.-
dc.languageengen_US
dc.publisherMedcom Limited. The Journal's web site is located at http://www.hkjpaed.org/index.asp-
dc.relation.ispartofHong Kong Journal of Paediatrics (New series)en_US
dc.titleDevelopment of Immunodominance Hierarchies Concurrent with Enhanced Polyfunctionality in T Cell Immunity Towards Epstein-Barr Virusen_US
dc.typeConference_Paperen_US
dc.identifier.emailChan, KH: chankh2@hkucc.hku.hken_US
dc.identifier.emailChiang, AKS: chiangak@hku.hken_US
dc.identifier.authorityChiang, AKS=rp00403en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros225084en_US
dc.identifier.volume18-
dc.identifier.issue4-
dc.identifier.spage253en_US
dc.identifier.epage253en_US
dc.publisher.placeHong Kong-

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