L'art suisse à Zurich

"Une petite nationale" au Kunsthaus de Zurich. Hodler, Vautier, Blanchet, Vallet, etc

Levels of CMV peptide specific CD8 T cells do not correlate with viremia.

<p>CMV specific CD8 T cells were quantified using peptide bound MHC class I pentamers. A Dotplots of an HLA-A2 and HLA-B7 positive patient with T cells reactive towards a total of four peptides are shown. B No association of CMV specific CD8 T cells or total CD8 T cells with the presence or absence of detectable viremia (p = 0.82 and p = 0.22, respectively). Bars indicate median T-cell numbers/µl. C CMV specific CD8 T-cell numbers towards individual peptides may show different kinetics over time within one individual. D Higher percentage of PD-1 expressing CD8 T cells in CMV specific CD8 T cells (recognizing HLA-A2 with peptide NLV and/or VLE) as compared to total CD8 T cells (p<0.0001). E No significant difference in the percentage of PD-1 expressing CD8 T cells in CMV specific CD8 T cells (recognizing HLA-A2 with peptide NLV) as compared to total CD8 T cells (p<0.19).</p

Patient characteristics.

<p>Abbreviations: BM, bone marrow; BU, busulfan; CY, cytoxin; FLU, fludarabin; MM, multiple myeloma; NHL, non-Hodgkin's lymphoma; PBSC, peripheral blood stem cells; TBI, total body irradiation.</p

Lowest levels of CMV specific CD4 T cells at the onset of and during viremia.

<p>A CMV specific or B total CD4 T cells were quantified in non-viremic individuals and compared to patients >14 days, <14 days, at the onset of, during, or after viremia. Bars indicate median numbers of cells/µl whole blood. Each patient is depicted once in a given time period. If more than one data set existed, mean values were calculated for each patient. The level of significance in the post-test (p<0.05, p<0.01, p<0.001) is depicted by one, two or three stars, respectively. C Inverse correlation between the levels of CMV specific CD4 T cells at onset of viremia and peak viral load thereafter (r = −0.45, p = 0.02).</p

Combined immunosuppression with cyclosporine A and methylprednisolone contributes to a decrease in CMV specific CD4 T-cell function.

<p>CMV specific CD4 T cells reactivity from six immunocompetent CMV seropositive individuals were analyzed directly from whole blood supplemented with or without 180 ng/ml cyclosporine A (CyA) in the absence or presence of increasing dosages of methylprednisolone (MP). A The mean percentage of IFN-γ producing CD4 T cells (including standard error of the mean, SEM) and B the mean percentage of BrdU positive, proliferating CD4 T cells (including SEM) was analyzed after 36 h of stimulation using flow-cytometry.</p

The percentage of ESAT-6 and CFP-10 specific IFN-γ/IL-2 dual positive CD4 T cells does not allow clear distinction between active tuberculosis (A-TB) and non-active disease states (T-TB or latent <i>M. tuberculosis</i> infection).

<p>This is evident from the fact that 7 of 12 (58%) of latently infected subjects had <56% IFN-γ/IL-2 dual positive ESAT-6-specific CD4 T cells The percentage of dual positive CD4 T cells specific for ESAT-6 and CFP-10 was determined as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017813#pone-0017813-g002" target="_blank">figure 2</a>. As compared with PPD specific profiles with higher overall frequencies, robust determination of profiles specific for ESAT-6 and CFP-10 could only be determined if overall frequencies of specific cells were above 0.1% (i.e. in 62.5% of patients with active tuberculosis, 35.7% of individuals with successfully treated disease and 56.0% of latently infected individuals). The stippled line indicates the 56% threshold established for PPD specific T cells.</p

Predominance of dual positive cytokine producing cells in non-active disease states.

<p>The percentages of cells expressing IFN-γ only, IL-2 only, and dual-cytokine producing CD4 T cells after PPD specific stimulation in individuals with immunity consistent with latent <i>M. tuberculosis</i> infection (<b>A</b>) or BCG vaccination/NTM infection (<b>B</b>) were determined as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017813#pone-0017813-g002" target="_blank">figure 2</a>.</p

The frequency of antigen-reactive CD4 T cells does not allow distinction between patients with active tuberculosis (A-TB) and successfully treated disease (T-TB).

<p>Whole blood from all individuals was stimulated with PPD, ESAT-6, or CFP-10 and antigen-specific CD4 T cells co-expressing CD69, IFN-γ and/or IL-2 were quantified using flow-cytometry. Although the difference in PPD reactive CD4 T-cell frequencies between the two groups was significant (p = 0.02, Mann-Whitney test), it was impossible to correctly assign the patients' clinical status on an individual basis. The median is depicted by the line.</p

Higher increase in PPD-reactive T cell frequencies in patients without pre-existing immunity before therapy.

<p>The increase of PPD and SEB-reactive CD69 positive IFN-γ producing T cells between baseline and the maximum value during BCG-instillations was quantified for all patients and results were stratified for patients with negative and positive PPD-status before therapy. Medians and interquartile ranges are indicated.</p

Demographic and clinical characteristics of patients with active and successfully treated tuberculosis.

<p>*including one patient with pleural tuberculosis.</p