Immune responses to human cytomegalovirus (HCMV) reactivation in allogeneic haematopoietic stem cell transplantation (HSCT)

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Hassan, Norfarazieda (2020). Immune responses to human cytomegalovirus (HCMV) reactivation in allogeneic haematopoietic stem cell transplantation (HSCT). University of Birmingham. Ph.D.

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Abstract

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is commonly used to treat a range of haematological malignancies with Human cytomegalovirus (HCMV) reactivation as one of the major risk factors. HCMV reactivation is crucial as it can lead to HCMV disease and increase mortality. The CMV serostatus of the recipient and donor in the HSCT setting plays a role in determining the risk of the patient getting viral reactivation. Recent studies have also suggested that CMV reactivation after HSCT is associated with faster immune reconstitution and reduction of leukaemia relapse. This project studied the phenotype kinetics of immune cells including Natural Killer (NK) cells, CD4\(^+\), CD8\(^+\) and TCR\(\gamma\delta\) T cells in HSCT patients after CMV reactivation. Also, the tetramer technique was used to study CMV specific CD8\(^+\) and CD4\(^+\) T cells responses reconstitution in these HSCT patients. Our data show that CMV reactivation gives significant impact on immune reconstitution of allo-HSCT by imprinting the immune cells with phenotypes specific to CMV. One major impact on NK cells seen in allo-HSCT with CMV reactivation is the huge expansion of CD56\(^{dim}\)CD16\(^{bright}\) NKG2C\(^+\) NK cells or the controversial ‘memory-like’ NK cells. The expansion of this NK population results in enhanced cytokines production after stimulation. In overall, the study of CMV reactivation in HSCT will ultimately give some insight of how to modify the clinical practice to target CMV reactivation and improve the overall clinical outcome.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
Supervisor(s):
Supervisor(s)EmailORCID
Moss, Paul A.UNSPECIFIEDUNSPECIFIED
Zuo, JianminUNSPECIFIEDUNSPECIFIED
Licence: All rights reserved
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: Institute of Cancer and Genomic Sciences
Funders: Other
Other Funders: Ministry of Higher Education and Universiti Sains Malaysia, Bloodwise
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
URI: http://etheses.bham.ac.uk/id/eprint/9949

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