Author Description

This dissertation, "Study of Epstein-barr Virus (EBV)-specific Polyfunctional T Cells Responses in Long Term Carriers and Patients With Infectious Mononucleosis and Haemophagocytic Lymphohistiocytosis" by Jia, Ning,, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Effective control of chronic viral infections may require the generation of polyfunctional T cells (PFCs) which are capable of producing multiple cytokines and possess cytotoxic function. In this study, I investigate (i) whether PFCs play an important role in the long term immune control of a persistent human virus, Epstein-Barr virus (EBV), (ii) the relationship between the development of immunodominance and functionality during the evolution of the anti-viral T cell responses, and (iii) whether PFCs can be generated in patients with EBV-associated haemophagocytic lymphohistiocytosis (HLH). To tackle the first question, I established a 9-color flow cytometry assay to characterize the co-expression of four cytokines (interferon-f [IFN-[], macrophage inflammatory protein 1-] [MIP1-[], tumour necrosis factor-] [TNF- ] and interleukin-2 [IL-2]) and degranulation marker (CD107a) by both EBV lytic and latent peptide-specific CD4+ and CD8+ T cells in 20 healthy long term viral carriers. Two patients with EBV-associated post-transplant lymphoproliferative disorder (PTLD) were studied for comparison. Both CD4+ and CD8+ PFCs were readily generated in the long term carriers with the immunodominant EBV proteins apparently stimulating higher proportions of PFCs than the subdominant viral proteins. The PFCs producing greater amount of cytokines per cell