Blood CXCR3(+) CD4 T Cells Are Enriched in Inducible Replication Competent HIV in Aviremic Antiretroviral Therapy-Treated Individuals

We recently demonstrated that lymph nodes (LNs) PD-1+/T follicular helper (Tfh) cells from antiretroviral therapy (ART)-treated HIV-infected individuals were enriched in cells containing replication competent virus. However, the distribution of cells containing inducible replication competent virus has been only partially elucidated in blood memory CD4 T-cell populations including the Tfh cell counterpart circulating in blood (cTfh). In this context, we have investigated the distribution of (1) total HIV-infected cells and (2) cells containing replication competent and infectious virus within various blood and LN memory CD4 T-cell populations of conventional antiretroviral therapy (cART)-treated HIV-infected individuals. In the present study, we show that blood CXCR3-expressing memory CD4 T cells are enriched in cells containing inducible replication competent virus and contributed the most to the total pool of cells containing replication competent and infectious virus in blood. Interestingly, subsequent proviral sequence analysis did not indicate virus compartmentalization between blood and LN CD4 T-cell populations, suggesting dynamic interchanges between the two compartments. We then investi-gated whether the composition of blood HIV reservoir may reflect the polarization of LN CD4 T cells at the time of reservoir seeding and showed that LN PD-1+ CD4 T cells of viremic untreated HIV-infected individuals expressed significantly higher levels of CXCR3 as compared to CCR4 and/or CCR6, suggesting that blood CXCR3-expressing CD4 T cells may originate from LN PD-1+ CD4 T cells. Taken together, these results indicate that blood CXCR3-expressing CD4 T cells represent the major blood compartment con-taining inducible replication competent virus in treated aviremic HIV-infected individuals

Combined Use of Mycobacterium tuberculosis-Specific CD4 and CD8 T-Cell Responses Is a Powerful Diagnostic Tool of Active Tuberculosis

Immune-based assays are promising tools to help to formulate diagnosis of active tuberculosis. A multiparameter flow cytometry assay assessing T-cell responses specific to Mycobacterium tuberculosis and the combination of both CD4 and CD8 T-cell responses accurately discriminated between active tuberculosis and latent infectio

Mixed Th1 and Th2 Mycobacterium tuberculosis-specific CD4 T cell responses in patients with active pulmonary tuberculosis from Tanzania.

Mycobacterium tuberculosis (Mtb) and helminth infections elicit antagonistic immune effector functions and are co-endemic in several regions of the world. We therefore hypothesized that helminth infection may influence Mtb-specific T-cell immune responses. We evaluated the cytokine profile of Mtb-specific T cells in 72 individuals with pulmonary TB disease recruited from two Sub-Saharan regions with high and moderate helminth burden i.e. 55 from Tanzania (TZ) and 17 from South Africa (SA), respectively. We showed that Mtb-specific CD4 T-cell functional profile of TB patients from Tanzania are primarily composed of polyfunctional Th1 and Th2 cells, associated with increased expression of Gata-3 and reduced expression of T-bet in memory CD4 T cells. In contrast, the cytokine profile of Mtb-specific CD4 T cells of TB patients from SA was dominated by single IFN-γ and dual IFN-γ/TNF-α and associated with TB-induced systemic inflammation and elevated serum levels of type I IFNs. Of note, the proportion of patients with Mtb-specific CD8 T cells was significantly reduced in Mtb/helminth co-infected patients from TZ. It is likely that the underlying helminth infection and possibly genetic and other unknown environmental factors may have caused the induction of mixed Th1/Th2 Mtb-specific CD4 T cell responses in patients from TZ. Taken together, these results indicate that the generation of Mtb-specific CD4 and CD8 T cell responses may be substantially influenced by environmental factors in vivo. These observations may have major impact in the identification of immune biomarkers of disease status and correlates of protection

Approximation des moments par l'utilisation de la théorie des fonctions analytiques

In this thesis, I define and explain the notion of punctual analytical uniform development (DUAP) versus moments or cumulants approximation of punctual uniforms analyticals 's class statistics. Hence, I derive "truncated" DUAP's version for numerical computation and implementation which called finite DUAP (F-DUAP). Using F-DUAP approximation lead to an error which was estimated. Due to nature's one of axiom of UAP statistics, the concept extension of DUAP method, to an other class statistic is limited. So, a new local theoretical concept was defined named analytical uniform development (DUA). This generalization let all derived DUAP's theorems become more general. Automatic differentiation and F-DUAP allow the implementation of DUAP or DUA method's on computer: I write the CUMAD and CUMADG codes that make the methods of a practical use. By, the programme CUMAD, I valid the utility of DUAP method, when I applied it to the approximation to moments of "weighted sum of squares statistic"

Surface deterioration of dental materials after simulated toothbrushing in relation to brushing time and load.

OBJECTIVES: (1) To evaluate the changes in surface roughness and gloss after simulated toothbrushing of 9 composite materials and 2 ceramic materials in relation to brushing time and load in vitro; (2) to assess the relationship between surface gloss and surface roughness. METHODS: Eight flat specimens of composite materials (microfilled: Adoro, Filtek Supreme, Heliomolar; microhybrid: Four Seasons, Tetric EvoCeram; hybrid: Compoglass F, Targis, Tetric Ceram; macrohybrid: Grandio), two ceramic materials (IPS d.SIGN and IPS Empress polished) were fabricated according to the manufacturer's instructions and optimally polished with up to 4000 grit SiC. The specimens were subjected to a toothbrushing (TB) simulation device (Willytec) with rotating movements, toothpaste slurry and at three different loads (100g/250g/350g). At hourly intervals from 1h to 10h TB, mean surface roughness Ra was measured with an optical sensor and the surface gloss (Gl) with a glossmeter. Statistical analysis was performed for log-transformed Ra data applying two-way ANOVA to evaluate the interaction between load and material and load and brushing time. RESULTS: There was a significant interaction between material and load as well as between load and brushing time (p<0.0001). The microhybrid and hybrid materials demonstrated more surface deterioration with higher loads, whereas with the microfilled resins Heliomolar and Adoro it was vice versa. For ceramic materials, no or little deterioration was observed over time and independent of the load. The ceramic materials and 3 of the composite materials (roughness) showed no further deterioration after 5h of toothbrushing. Mean surface gloss was the parameter which discriminated best between the materials, followed by mean surface roughness Ra. There was a strong correlation between surface gloss and surface roughness for all the materials except the ceramics. The evaluation of the deterioration curves of individual specimens revealed a more or less synchronous course suspecting hinting specific external conditions and not showing the true variability in relation to the tested material. SIGNIFICANCE: The surface roughness and gloss of dental materials changes with brushing time and load and thus results in different material rankings. Apart from Grandio, the hybrid composite resins were more prone to surface changes than microfilled composites. The deterioration potential of a composite material can be quickly assessed by measuring surface gloss. For this purpose, a brushing time of 10h (=72,000 strokes) is needed. In further comparative studies, specimens of different materials should be tested in one series to estimate the true variability

+CD4 T Cells Are Enriched in Inducible Replication Competent HIV in Aviremic Antiretroviral Therapy-Treated Individuals

+CD4 T cells. Taken together, these results indicate that blood CXCR3-expressing CD4 T cells represent the major blood compartment containing inducible replication competent virus in treated aviremic HIV-infected individual

Functional profile and expression of co-stimulatory molecules and of co-inhibitory receptors of HIV-specific CD8 T-cell responses during acute and chronic HIV infections.

<p>Analysis of the functional profile (<b>A</b>), of the expression of CD27 and CD28 (<b>B</b>) and of the expression of 2B4, CD160 and PD-1 (<b>C</b>) in HIV-specific CD8 T cells in patients with acute (PHI-B), untreated chronic progressive (CP-B) or non-progressive (LTNP) HIV infection. Representative examples of the distinct flow cytometry panels are shown in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003423#ppat.1003423.s001" target="_blank">Fig. S1B</a>-D. Regarding the functional profile (<b>A</b>), although TNF-α was detected, analyses are restricted to the expression of IFN-γ, IL-2 and perforin for clarity. All possible combinations of the distinct markers are shown on the <i>x</i> axis, whereas the percentages of the distinct cell subsets within virus-specific CD8 T cells are shown on the <i>y</i> axis. The pie charts summarize the data, and each slice corresponds to a certain combination of molecules. Colors in the pie charts are based on the colored boxes at the bottom of the panel.</p

Increased CDR3 renewal of HIV-specific CD8 T cells following treatment interruption and association with functional avidity.

<p><b>A.</b> Percentage of CDR3 renewal of HIV-specific CD8 T cells before (under treatment) and after treatment interruption (TI). CDR3 diversity and renewal were determined as described <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003423#ppat.1003423-Miconnet1" target="_blank">[32]</a>. Example of TRBV usage and CDR3 size pattern analysis of B*0702-_GPGHKARVL-specific CD8 T cells in patient #1023 at week 18, 96 and 125 are shown in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003423#ppat.1003423.s003" target="_blank">Fig. S3</a>. <b>B.</b> Association between the percentage of CDR3 renewal and changes in the functional avidity of HIV-specific CD8 T cells.</p

Qualitative changes of HIV-specific CD8 T cells in patients experiencing a virus rebound following treatment interruption.

<p><b>A.</b> Longitudinal analysis of the CD4 T-cell counts and HIV viremia of 2 representative HIV-infected patients (#1017 and #1023) treated with ART since acute infection. Patient #1017 remained on ART, whereas patient #1023 spontaneously interrupted ART after 119 weeks (orange box). <b>B.</b> Functional profiles of B*0702-_GPGHKARVL-specific CD8 T cells from patients #1017 and #1023 analyzed at two distinct time-points corresponding to weeks 48 and 300 (identified by the arrows in A). <b>C.</b> Cumulative analysis of the functional profile of HIV-specific CD8 T-cell responses on the basis of the expression of IFN-γ, IL-2 and perforin in patients with acute (PHI) infection after one year of ART (-T1Y) and after either treatment interruption (-ATI) or after five years of ART (-T5Y). Matched-paired HIV-specific CD8 T-cell responses are considered for the comparison between T1Y and ATI or between T1Y and T5Y. Although TNF-α was also detected, analysis is restricted to the expression of IFN-γ, IL-2 and perforin for clarity. All possible combinations of IFN-γ, IL-2 and perforin are shown on the <i>x</i> axis, whereas the percentages of the distinct cell subsets within HIV-specific CD8 T cells are shown on the <i>y</i> axis. The pie charts summarize the data, and each slice corresponds to a certain combination of functions. Colors in the pie charts are based on the colored boxes at the bottom of the panel. <b>D.</b> PD-1 expression in B*0702-_GPGHKARVL-specific CD8 T cells in patients #1017 and #1023 measured at the two time-points identified with arrows in A. <b>E.</b> Mean fluorescence intensity (MFI) of PD-1 expression in HIV-specific CD8 T cells measured in patients with acute (PHI) HIV infection after 1 year of ART (-T1Y) and after either treatment interruption (-ATI, left panel) or after five years of ART (-T5Y, right panel). <b>F.</b> Proportion of PD-1⁺2B4⁺CD160⁺ cells in B*0702-_GPGHKARVL-specific CD8 T cells in patients #1017 and #1023 measured at the two time-points identified with arrows in A. <b>G.</b> Proportion of PD-1⁺2B4⁺CD160⁺ cells in HIV-specific CD8 T cells measured in patients with acute (PHI) HIV infection after 1 year of ART (-T1Y) and after either treatment interruption (-ATI, left panel) or after five years of ART (-T5Y, right panel).</p