Essa, Sahar Sultan (2001) A study on the cell mediated immunity of human cytomegalovirus infection in kidney transplant recipients. PhD thesis, University of Warwick.

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Abstract

Cytomegalovirus (CMV) infection is a major complication after kidney transplantation. Despite antiviral therapy it contributes significantly to high morbidity. This study was aimed at (a) detecting· a CMV specific antigen pp65 in CMV -infected fibroblast cells and in leukocytes of kidney transplant recipients by flow cytometric assay (FCA) (b) determining the stimulation index (S.I.) of phytohaemagglutinin (PHA) and CMV-stimulated peripheral blood mononuclear cells (PBMC), (c) determining the levels of Th1- and Th-2 related cytokines in the supernatant of stimulated PBMC from kidney transplant recipients with and without active CMV infection (d) determining immunophenotyping of cells found in the peripheral blood of CMV -infected and CMV -uninfected kidney transplant recipients by flow cytometry using antibodies specific to CD2+ (pan T), CD3+ (mature T), CD4+ (T helper), CD8+ (T suppressor), CD26+(T activated), CDI6+/CDS6+ (NK cell), CDI9+(pan B), CDIS+ (granulocytes). Thirty-five patients with, and 44 without active CMV infections, as diagnosed by a CMV antigenemia assay (AA), were inducted into this study. FCA distinguished clearly between the infected and uninfected fibroblast cells. Regarding kidney transplant recipients, the FCA was positive when the number of AA positive cells was five or more per 5x10(4). Moreover, the percentage of antigenemia-positive cells by FCA correlated well with symptomatic CMV infections. After PHA and CMV stimulation of PBMC from patients, S.I. was determined by radioactive thymidine uptake while the production of Th1-type cytokines [interleukin-2 (iL-2), interferon-y (IFN-y) and tumor necrosis factor-a (TNFex)] and Th2-type cytokines (IL-4, IL-1O) were measured by ELISA. PBMC of patients with active CMV infection showed significantly lower S.I. values than patients without an ongoing CMV infection (p<O.OOO1). Levels of Th2- type cytokines in CMV -infected and uninfected kidney recipients were similar;however, the levels of the Th1-type cytokines were significantly lower in CMV -infected patients (p<O.O5). Low levels of Th1-type cytokines seem to correlate well with active CMV infection in kidney recipients. The percentage of CD3+ immunocompetent T lymphocytes and CD4+ T lymphocytes were consistently higher in kidney transplant recipients without an active CMV infection than in the group of recipients with an active CMV infection. These differences were statistically significant in the case of CD3+ (p<O.O5) and CD4+ (p<O.OO5). On the other hand the difference in percentage CD2+, CD8+, CD16++CD56+, CD19+, CD15+ cells were statistically insignificant. Therefore, these data suggest that active CMV infection in kidney transplant recipients is associated with a significant alteration in the lymphocyte proliferative responses, the levels of Th1-type cytokines (IFN-y, TNF-ex, IL-2), and the percentage of CD3+, CD4+ when compared to kidney transplant recipients without active CMV infection.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QH Natural history > QH301 Biology R Medicine > R Medicine (General)
Library of Congress Subject Headings (LCSH):	Cytomegalovirus infections, Kidneys -- Transplantation, Immune system
Official Date:	March 2001
Dates:	Date Event March 2001 Submitted
Institution:	University of Warwick
Theses Department:	Department of Biological Sciences
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Easton, A. J. (Andrew J.)
Extent:	151, [vi] leaves
Language:	eng

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