Human Leucocyte Antigen G Expression in Cytomegalovirus Infection in Normal Individuals and Renal Transplant Patients



Al-Bayati, ZM
(2017) Human Leucocyte Antigen G Expression in Cytomegalovirus Infection in Normal Individuals and Renal Transplant Patients. PhD thesis, University of Liverpool.

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Abstract

HLA-G is a non-classical human MHC I molecule which is abundantly expressed in trophoblast during pregnancy. This molecule is also expressed by several leucocyte subsets but on a low percentage of cells. It can also be secreted in soluble form. The protein is upregulated in several conditions like viral infections, autoimmune disorders and tumours. Several reports have indicated the expression of HLA-G is associated with allograft acceptance and survival. This study was aimed at investigating the expression of HLA-G and its ligand, KIR2DL4, in association with other activation markers, particularly CD103, BAFF and BAFF-R, in relation to CMV antigen stimulation in healthy subjects. Also, HLA-G and KIR2DL4 expression and their association with genotype were studied in renal transplant patients before and after transplantation. HLA-G was expressed by a significantly higher proportion of CD19+ B cells and CD56+ T cells following stimulation of peripheral blood mononuclear cells (PBMCs) from CMV+ healthy subjects with CMV antigen. Also, sHLA-G levels were significantly elevated in PBMC supernatants from CMV+ subjects stimulated with CMV antigen. The HLA-G ligand KIR2DL4 was significantly upregulated in IL-2 culture on CD56+ T cells and significantly downregulated in CD56bright cells. Induction of PBMCs with CMV antigens significantly increased the proportion of CD8+ T cells, NK cells and CD56+ cells T cells expressing this ligand. Also, proportions of HLA-G+CD103+ T cells were significantly increased following CMV stimulation. Stimulation of PBMCs with CMV antigen demonstrated significantly increased proportions of BAFF-R+ CD56+ cells and significantly decreased proportions of BAFF-R+ B cells. HLA-G was expressed on a significantly greater proportion of BAFF+ and BAFF-R+ cells following CMV stimulation. In renal transplant patients, HLA-G was expressed on a significantly higher proportion of CD4+ cells and monocytes as well as B cells following transplantation. However, KIR2DL4 was significantly upregulated only on CD56dim cells following transplantation. Finally, culture of PBMCs with the standard immunosuppressive drugs used in transplant patients did not generally inhibit or augment the effects of CMV on HLA-G, CD103, BAFF and BAFF-R expression by PBMCs from healthy subjects, apart from CD4+ cells and CD56+ cells of which significantly greater proportions expressed HLA-G in response to tacrolimus (Prograf) in combination with CMV particles. Also, CD103 was expressed by significantly higher proportions of these cells in the same treatment combination. In conclusion, the results are consistent with CMV enhancing HLA-G expression on several cell types which may play an important role to allow immune escape during virus infection. In renal transplant patients, proportions of HLA-G+ cells increased significantly in several cell subpopulations after transplantation. Immunosuppressive drug treatment may have contributed to this.

Item Type: Thesis (PhD)
Divisions: Fac of Health & Life Sciences > Faculty of Health and Life Sciences
Depositing User: Symplectic Admin
Date Deposited: 21 Aug 2018 10:26
Last Modified: 05 Mar 2021 08:10
DOI: 10.17638/03019793
Supervisors:
  • Christmas, Steve
  • Flanagan, Brian
  • Meddleton, Derek
URI: https://livrepository.liverpool.ac.uk/id/eprint/3019793