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Excision Circles (excision + circle)

Distribution by Scientific Domains
Medical Sciences87%

Kinds of Excision Circles

  • receptor excision circle
    		•

    Selected Abstracts

    Evaluation of the impact of highly active antiretroviral therapy on immune recovery in antiretroviral naive patients

    HIV MEDICINE, Issue 1 2004
    L Al-Harthi
    Objectives To examine the extent of immune reconstitution in treatment-naive patients with CD4 T-cell counts <500 cells/,L following 48 weeks of highly active antiretroviral therapy (HAART). Methods Thirteen antiretroviral naive patients were evaluated longitudinally for 48 weeks on HAART utilizing immune functional and lymphocyte phenotyping assays, including lymphocyte proliferation assay, flow cytometric evaluation of cell surface markers, and delayed type hypersensitivity skin tests. Virologic responses were monitored using commercially available viral load assays and gag/pol mRNA quantification using simultaneous immunophenotyping/UltraSensitive fluorescence in situ hybridization (ViroTect In Cell HIV-1 Detection Kit; Invirion, Frankfort, MI). Thymic function was evaluated for a subset of four patients using real-time polymerase chain reaction (PCR) for T-cell receptor excision circle (TREC) quantification and thymic scans using computerized axial tomography (CT) of the thymus. Results HAART initiation resulted in a significant decline in plasma viremia and percentage of infected peripheral blood cells, and a rise in CD4 T cells from a baseline median of 207 cells/,L to a week-48 median of 617 cells/,L. The rise was predominately in CD4 memory cells. Naive T cells also increased in number, but at a slower rate. Activated (HLA-DR CD38) CD4 and CD8 T cells were elevated at baseline (24 and 62%, respectively) and declined by week 48 (17 and 36%, respectively) but did not reach normal levels. The number of Fas CD4 T cells increased from a baseline median of 169 to 381 cells/,L at week 48. Both soluble interleukin (IL)-2 and tumour necrosis factor (TNF) II receptors declined by week 48. HIV p24 lymphocyte proliferation assay responses were transiently detected in three patients. TREC values increased from a median 6400 copies/,g at baseline to a week-48 median value of 26 697 copies/,g. Conclusion Immune functional reconstitution was not achieved in these HAART naive patients. [source]

    Determining thymic output quantitatively: using models to interpret experimental T-cell receptor excision circle (TREC) data

    IMMUNOLOGICAL REVIEWS, Issue 1 2007
    Ruy M. Ribeiro
    Summary:, T cells develop in the thymus and then are exported to the periphery. As one ages, the lymphoid mass of the thymus decreases, and a concomitant decrease in the ability to produce new T cells results. Human immunodeficiency virus (HIV) infects CD4+ T cells and, hence, can also affect thymic function. Here we discuss experimental techniques and mathematical models that aim to quantify the rate of thymic export. We focus on a recent technique involving the quantification of T-cell receptor excision circles (TRECs). We discuss how proper interpretation of TREC data necessitates the critical development of appropriate mathematical models. We review the theory for interpretation of TREC data during aging, HIV infection, and anti-retroviral treatment. Also, we show how TRECs can be used to accurately quantify thymic output in the context of thymectomy experiments. We show that mathematical models are not only useful but absolutely necessary for these analyses. As such, they should be taken as just another tool in the immunologist's arsenal. [source]

    Evidence of thymic reconstitution after highly active antiretroviral therapy in HIV-1 infection

    HIV MEDICINE, Issue 2 2004
    G Hardy
    Objectives We aimed to provide evidence of thymic reconstitution after highly active antiretroviral therapy (HAART) in HIV-1 infected patients and to correlate this with the restoration of peripheral naïve T cells. Methods Positron emission tomography (PET) enables definitive evidence of thymic activity, indicating functional potential. In this case study, a single patient who initiatiated HAART demonstrated reconstitution of the naïve T-cell pool and underwent thymic PET scans at baseline and 2 and 6 months following initiation of therapy. Two patients who failed to demonstrate such reconstitution acted as controls. These patients (mean age 27 years) had chronic HIV infection with low CD4 T-cell counts (mean 82, range 9,160 cells/,L blood). Increased function of the thymus visualized by PET was correlated with phenotypic changes in CD4 and CD8 T cells in the periphery measured by flow cytometry, and with numbers of recent thymic emigrants measured by quantification of the numbers of T-cell receptor excision circles (TRECs) in peripheral cells. Results In one patient, clear correlations could be drawn between visible activity within the thymus, as measured by increased [F18]fluorodeoxyglucose (FDG) uptake, and regeneration of naïve CD4 (CD45RA/CD62L) T cells, increased numbers of CD4 T cells, controlled viraemia and increased numbers of recent thymic emigrants. A second patient displayed no increase in peripheral CD4 count and no increase in thymic activity. The third patient elected to stop therapy following the 2-month time point. Conclusions The use of PET suggests that thymic activity may increase after HAART, indicating that the thymus has the potential to be functional even in HIV-1 infected persons with low CD4 T-cell counts. [source]

    Determining thymic output quantitatively: using models to interpret experimental T-cell receptor excision circle (TREC) data

    IMMUNOLOGICAL REVIEWS, Issue 1 2007
    Ruy M. Ribeiro
    Summary:, T cells develop in the thymus and then are exported to the periphery. As one ages, the lymphoid mass of the thymus decreases, and a concomitant decrease in the ability to produce new T cells results. Human immunodeficiency virus (HIV) infects CD4+ T cells and, hence, can also affect thymic function. Here we discuss experimental techniques and mathematical models that aim to quantify the rate of thymic export. We focus on a recent technique involving the quantification of T-cell receptor excision circles (TRECs). We discuss how proper interpretation of TREC data necessitates the critical development of appropriate mathematical models. We review the theory for interpretation of TREC data during aging, HIV infection, and anti-retroviral treatment. Also, we show how TRECs can be used to accurately quantify thymic output in the context of thymectomy experiments. We show that mathematical models are not only useful but absolutely necessary for these analyses. As such, they should be taken as just another tool in the immunologist's arsenal. [source]

    Thiazolidinedione treatment and constitutive-PPAR, activation induces ectopic adipogenesis and promotes age-related thymic involution

    AGING CELL, Issue 4 2010
    Yun-Hee Youm
    Summary Age-related thymic involution is characterized by reduction in T cell production together with ectopic adipocyte development within the hematopoietic and thymic niches. Peroxisome proliferator-activated receptor gamma (PPAR,) is required for adipocyte development, glucose homeostasis and is a target for several insulin-sensitizing drugs. Our prior studies showed that age-related elevation of PPAR, expression in thymic stromal cells is associated with thymic involution. Here, using clinically relevant pharmacological and genetic manipulations in mouse models, we provide evidence that activation of PPAR, leads to reduction in thymopoiesis. Treatment of aged mice with antihyperglycemic PPAR,-ligand class of thiazolidinedione drug, rosiglitazone caused robust thymic expression of classical pro-adipogenic transcripts. Rosiglitazone reduced thymic cellularity, lowered the naïve T cell number and T cell receptor excision circles (TRECs) indicative of compromised thymopoiesis. To directly investigate whether PPAR, activation induces thymic involution, we created transgenic mice with constitutive-active PPAR, (CA-PPARg) fusion protein in cells of adipogenic lineage. Importantly, CA-PPAR, transgene was expressed in thymus and in fibroblast-specific protein-1/S100A4 (FSP1+) cells, a marker of secondary mesenchymal cells. The CAPPAR, fusion protein mimicked the liganded PPAR, receptor and the transgenic mice displayed increased ectopic thymic adipogenesis and reduced thymopoiesis. Furthermore, the reduction in thymopoiesis in CA-PPAR, mice was associated with higher bone marrow adiposity and lower hematopoietic stem cell progenitor pool. Consistent with lower thymic output, CAPPAR, transgenic mice had restricted T cell receptor repertoire diversity. Collectively, our data suggest that activation of PPAR, accelerates thymic aging and thymus-specific PPAR, antagonist may forestall age-related decline in T cell diversity. [source]

    Premature aging of the immune system in children with juvenile idiopathic arthritis

    ARTHRITIS & RHEUMATISM, Issue 7 2008
    Martina Prelog
    Objective Juvenile idiopathic arthritis (JIA) is an autoimmune disease of the young. The pathogenesis is not completely understood. Premature aging, associated thymic involution, and compensatory autoproliferation could play important roles in the pathogenesis of autoimmunity. We undertook this study to determine whether patients with JIA demonstrate premature immunosenescence. Methods To test this hypothesis, we measured 3 indicators of aging: the percentages and total counts of peripheral blood naive T cells, the frequency of T cell receptor excision circles (TRECs) in naive T cells, and telomeric erosion and Ki-67 expression as estimates of the replicative history of homeostatic proliferation. Results JIA patients showed an accelerated loss of CD4+,CD45RA+,CD62L+ naive T cells with advancing age and a compensatory increase in the number of CD4+,CD45RO+ memory T cells. JIA patients demonstrated a significantly decreased frequency of TRECs in CD4+,CD45RA+ naive T cells compared with age-matched healthy donors (P = 0.002). TREC numbers correlated with age only in healthy donors (P = 0.0001). Telomeric erosion in CD4+,CD45RA+ naive T cells was increased in JIA patients (P = 0.01). The percentages of Ki-67,positive CD4+,CD45RA+ naive T cells were increased in JIA patients (P = 0.001) and correlated with disease duration (P = 0.003), which was also an independent factor contributing to telomeric erosion (P = 0.04). Conclusion Our findings suggest that age-inappropriate T cell senescence and disturbed T cell homeostasis may contribute to the development of JIA. In patients with JIA, dysfunction in the ability to reconstitute the T cell compartment should be considered when exploring new therapeutic strategies. [source]

    Tracing thymic output in older individuals

    CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2010
    W. A. Mitchell
    Summary As a result of age-associated thymic atrophy, T cell production declines with age. Some studies suggest that production undergoes an exponential decline starting at birth, while others consider the decline to be in a biphasic manner with a rapid reduction in output occurring before middle age followed by a phase in which output declines at a regular, albeit much slower, rate. Both approaches provide estimations of the time of termination of thymic output, but on the basis of limited amounts of data. We have analysed blood from more than 200 individuals between the ages of 58 and 104 years to determine changes in thymic output using signal-joint T cell receptor excision circles (sjTREC)/T cells as our measure. To reduce any potential geographical or nutritional bias we have obtained samples from five different European countries. Our results reveal that while the absolute number of T cells per microlitre of blood does not change significantly across the age range we tested, the values of sjTREC per microlitre show wide variation and reveal an age-associated decline in thymic output. In addition we show gender differences, with notably higher thymic output in females than males at each decade. More importantly, we noted a significant decline in sjTREC/T cell levels in those more than 90 years of age in both males and females. Our results provide information about the potential end-point for thymic output and suggest that sjTREC analysis may be a biomarker of effective ageing. [source]

    Homeostatic role of IL-7 in HIV-1 infected children on HAART: Association with immunological and virological parameters

    ACTA PAEDIATRICA, Issue 2 2005
    S Resino
    Abstract Aim: To investigate the role of IL-7 in HIV-infected children on highly active antiretroviral therapy (HAART) and its association with laboratory parameters related to disease progression. Patients and methods: A cross-sectional study in 31 vertically HIV-infected children (median age 8.4 y) treated with HAART, and a longitudinal study in four of those same children was carried out. In both studies, viral load, CD4+ T-cell counts, thymic production of T cells by TCR rearrangement excision circles (TRECs), IL-7 plasma levels and viral phenotype were determined. Results: IL-7 levels were higher in HIV-infected children than in age-matched, uninfected controls. In addition, HIV children with CD4+ T cells between 200 and 500 T cells/mm3 had higher IL-7 levels and lower TREC values than HIV-infected children with CD4+ T cells >500 T cells/mm3. IL-7 levels were higher in children with syncytium-inducing (SI) phenotype than in those with non-syncytium-inducing (NSI) variants. During the follow-up of four HIV children, the decrease in viral load after HAART was always associated with a recovery of CD4+ T cells and TRECs, which was followed by a decrease in IL-7 returning to the levels present prior to the drop in CD4+ T cells. The four HIV-infected children had SI/X4 isolates in PBMC before HAART, and the viral phenotype switched to NSI/R5 after HAART. Conclusion: Our data suggest that IL-7 plays a key role in the maintenance of T-cell homeostasis in HIV-infected children on HAART, both through peripheral expansion and through a thymus-dependent mechanism. [source]