Discriminating rejection from CMV infection in renal allograft recipients using flow cytometry

Siegel, Don L.; Fox, Ira J.; Dafoe, Donald C.; Power, Michelle; Asplund, Mark W.; Zellers, Lydia; Barker, Clyde F.; Prystowsky, Michael B.

doi:10.1016/0090-1229(89)90016-0

Cited by 13 publications

(7 citation statements)

References 41 publications

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“…ϩ T cell activation has been observed in HIVnegative children and transplant recipients with primary CMV infection (18,21,26,29,35). Cellular activation contributes to HIV-1 pathogenesis by a number of mechanisms (reviewed in references 9 and 16), including depletion of T cells via activationinduced cell death (AICD).…”

Section: An Increase In Cd8mentioning

confidence: 99%

Acute Cytomegalovirus Infection Is Associated with Increased Frequencies of Activated and Apoptosis-Vulnerable T Cells in HIV-1-Infected Infants

Slyker

Rowland‐Jones

Dong

et al. 2012

J Virol

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i Cytomegalovirus (CMV) coinfection is associated with infant HIV-1 disease progression and mortality. In a cohort of Kenyan HIV-infected infants, the frequencies of activated (CD38 ؉ HLA-DR ؉ ) and apoptosis-vulnerable (CD95 ؉ Bcl-2 ؊ ) CD4 ؉ and CD8 ؉ T cells increased substantially during acute CMV infection. The frequency of activated CD4 ؉ T cells was strongly associated with both concurrent CMV coinfection (P ‫؍‬ 0.001) and HIV-1 viral load (P ‫؍‬ 0.05). The frequency of apoptosis-vulnerable cells was also associated with CMV coinfection in the CD4 (P ‫؍‬ 0.02) and CD8 (P < 0.001) T cell subsets. Similar observations were made in HIV-exposed uninfected infants. CMV-induced increases in T cell activation and apoptosis may contribute to the rapid disease progression in coinfected infants.

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Section: An Increase In Cd8mentioning

confidence: 99%

Acute Cytomegalovirus Infection Is Associated with Increased Frequencies of Activated and Apoptosis-Vulnerable T Cells in HIV-1-Infected Infants

Slyker

Rowland‐Jones

Dong

et al. 2012

J Virol

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“…This increase occurred despite the presence of cyclosporine, a drug known to act as an inhibitor of antigen HLA-DR expression in lymphocytes (34,35). This suggests that the activation of T cells by virus induction is not inhibited by this drug.…”

Section: Discussionmentioning

confidence: 72%

Lymphocyte subpopulations during cytomegalovirus disease in renal transplant recipients

Castro

Sporleder

Schroeder

et al. 2003

Braz J Med Biol Res

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We have determined the number of circulating T, B and natural killer cells in renal transplant recipients in order to detect changes during cytomegalovirus (CMV) infections. Serial blood samples were taken from 61 patients on standard triple immunosuppression therapy (cyclosporin A, azathioprine and prednisone). Using two-color flow cytometry analysis, the absolute number of CD3+, CD4+, CD8+, CD19+, CD3+HLA-DR+ and CD16+56+ cells was determined. Fortyeight patients (78.7%) developed active CMV infection, and all of them subsequently recovered. Twenty of the infected patients (32.8%) presented symptoms compatible with CMV disease during the infectious process. The number of lymphocytes and their main subpopulations were normal before the onset of CMV disease. During the disease there was a decrease followed by a significant increase (P<0.005) in the number of CD3+, CD4+, CD8+ and CD3+HLA-DR+ cells. No significant changes were observed in natural killer cells or B lymphocytes during the disease. We conclude, as observed in all viremic patients recovering from infection, that recovery is associated with an increase in the number of T cell subsets. The monitoring of different lymphocyte subsets along with antigenemia can be extremely useful in the detection of patients at high risk of developing CMV symptoms, allowing the early introduction of antiviral therapy or the reduction of immunosuppression therapy. Correspondence

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“…Mott Children's Hospital at the University of Michigan Medical Center. Immunosuppressive induction, until August 1992, included MALG (20 mg/kg/d) for a 10 d course, in addition to preoperative intravenous solumedrol(l0 mg/kg) and azathioprine (Aza; 1.5 mg) as well as postoperative oral prednisone (P; 2 mg/kg/d with a taper to 0.5 mg/kg/d at 3 weeks), and Aza ( 2 mg/kg/d). Cyclosporine (CSA; 14 mg/ kg/d) is administered upon adequacy of renal function aiming for trough CSA levels of 100-125 ndml as measured by high performance liquid chromatography T-CELL SUBSETS IN PEDIATRIC RENAL TRANSPLANT (HPLC).…”

Section: Methodsmentioning

confidence: 99%

“…The use of immune monitoring by flow cytometry has been suggested by some to help in discriminating infectious complications from allograft rejection (19,20). If one were to increase the dose of the polyclonal agents then potentially more T-cell depletion would occur.…”

Section: Bunchman 20mentioning

confidence: 99%

Flow cytometry: Its use in pediatric renal transplantation utilizing polyclonal induction

Bunchman

1995

Cytometry

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Induction protocols for pediatric renal transplant recipients commonly utilize polyclonal or monoclonal agents in sequence with additional immunosuppression. Polyclonal agents Minnesota antilymphoblast globulin (MALG), anti-thymocyte globulin (ATGAM) effect both T and B cells while monoclonal agents (OKT3) are T-cell specific. Flow cytometric analysis of T-cell subsets has become the marker of adequacy of immunosuppression during OKT3 therapy, yet to date no marker exists to measure the adequacy of immunosuppression with polyclonal agents. At the University of Michigan, flow cytometric analysis in pediatric renal transplant recipients undergoing polyclonal induction reveals that CD3, CD4, and CD8 suppression initially occurs. As opposed to OKT3, a rebound of CD3 cells occurs despite daily use of a polyclonal agent in sequence with additional immunosuppressives. During these analyses, a single kidney was lost which flow cytometry failed to predict. No significant difference in flow cytometric patterns occurred when comparing ATGAM to MALG induction. Flow cytometry utilized during polyclonal induction in pediatric renal transplant recipients revealed a variety of T-cell suppression patterns but failed to demonstrate persistence of suppression. Despite this lack of suppression as indicated by flow cytometry, a 97% 1 year allograft survival rate exists in the pediatric transplant program at the University of Michigan Medical Center. Therefore, the role of flow cytometry during polyclonal induction has yet to be well defined. o 1995 Wiley-Liss, inc.Key terms: T-cell subsets, pediatric renal transplantation, immunosuppression CD3 suppression, as measured by flow cytometry, is the marker for the adequacy of therapy during the use of monoclonal antibody OKT3 (Ortho, Raritan, NJ) ( 1 ). CD4, as well as CD8, suppression does occur during the early stages of OKT3 administration, yet rebounds relatively early in the course. Polyclonal agents utilized in North America such as Minnesota antilymphoblast globulin (MALG) or ATGAM (Upjohn, Kalamazoo, MI) are other agents utilized in organ transplantation. A recent study at the University of Michigan revealed that CD3, CD4, as well as CD8 suppression occurs early during induction therapy with MALG in a pediatric renal transplant recipient. A tendency toward normalization of these T-cell subsets occurs by 4 or 5 d despite a 10 d course of MALG administration (2). Due to the unavailability of MALG, a transition from MALG to ATGAM induction has occurred both nationally as well as at the University of Michigan. N o pediatric data exist, to date, comparing the efficacy of MALG to ATGAM. Therefore, previous T-cell suppression of MALG cannot be extrapolated to ATGAM.Over the last 2.5 years we have evaluated T-cell subsets during induction therapy as measured by flow cytometry. Induction therapy in all cases has included the use of a polyclonal agent. Herein is a report of the use of flow 6 1995 Wiley-Liss, Inc cytometry during polyclonal induction in the pediatric renal recipient. Its ef...

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Discriminating rejection from CMV infection in renal allograft recipients using flow cytometry

Cited by 13 publications

References 41 publications

Acute Cytomegalovirus Infection Is Associated with Increased Frequencies of Activated and Apoptosis-Vulnerable T Cells in HIV-1-Infected Infants

Acute Cytomegalovirus Infection Is Associated with Increased Frequencies of Activated and Apoptosis-Vulnerable T Cells in HIV-1-Infected Infants

Lymphocyte subpopulations during cytomegalovirus disease in renal transplant recipients

Flow cytometry: Its use in pediatric renal transplantation utilizing polyclonal induction

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