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Monitoring CD69 expression in circulating t-lymphocytes following renal transplantation

University of British Columbia

Acute graft rejection is the most frequent barrier to successful renal transplantation. The rejection process begins when transplant recipient T-lymphocytes become activated by graftderived antigens, which causes these leukocytes to search for and eradicate the foreign organ. Studies were conducted to evaluate the surface expression of CD69, a T-cell activation marker, as an index of the immune status in renal transplant patients and as a potential diagnostic predictor of graft rejection. Peripheral blood lymphocytes were first stimulated in vitro with phytohaemagglutinin (PHA). The baseline and induced CD69 expression in principal T-cell subsets was measured by flow cytometry and compared between normal healthy individuals, end-stage renal failure patients undergoing either haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) therapy, and long-term stable kidney transplant patients (ST). New renal transplant recipients (NT) were monitored longitudinally during their first three post-transplant months. The temporal kinetics of CD69 expression and the effects of the immunosuppressive drug cyclosporin A (CsA) were also examined. Results indicated that circulating T-cells from healthy subjects expressed negligible levels of CD69. However, its expression was observed after 4 hours of PHA stimulation, with peak response occurring after 24 hours and declining to low levels rapidly after 72 hours. Based on this type of expression kinetics, CD69 was considered as an early marker of T-cell activation. CsA at concentrations that strongly suppressed T-cell blastogenesis only partially inhibited CD69 induction. Several significant variations in the CD69 expression of resting and 24-hr PHA-stimulated Tcells were observed between healthy controls and patients in HD, CAPD and ST groups. Most NT patients maintained a rejection-free post-transplant course, and their T-cells remained non-activated and CD69[sup low] . During the first two post-transplant weeks, CD69 induction was reduced to half of the pre-transplant values possibly due to the intense immunomodulation required for rejection prophylaxis. In summary, CD69 emerged as a robust T-cell activation marker since potent immunosuppression in vivo is required to curtail its induction effectively. Increased expression differentiated recently activated T-cells from resting ones. Hence, an increase in CD69- expressing T-cells in peripheral blood might represent an early indication of acute kidney allograft rejection.

Thesis/Dissertation

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2009-06-15

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http://hdl.handle.net/2429/9179

Experimental Medicine

University of British Columbia

UBCV

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