Loss of Receptor on Tuberculin-Reactive T-Cells Marks Active Pulmonary Tuberculosis

BACKGROUND: Tuberculin-specific T-cell responses have low diagnostic specificity in BCG vaccinated populations. While subunit-antigen (e.g. ESAT-6, CFP-10) based tests are useful for diagnosing latent tuberculosis infection, there is no reliable immunological test for active pulmonary tuberculosis. Notably, all existing immunological tuberculosis-tests are based on T-cell response size, whereas the diagnostic potential of T-cell response quality has never been explored. This includes surface marker expression and functionality of mycobacterial antigen specific T-cells. METHODOLOGY/PRINCIPAL FINDINGS: Flow-cytometry was used to examine over-night antigen-stimulated T-cells from tuberculosis patients and controls. Tuberculin and/or the relatively M. tuberculosis specific ESAT-6 protein were used as stimulants. A set of classic surface markers of T-cell naive/memory differentiation was selected and IFN-gamma production was used to identify T-cells recognizing these antigens. The percentage of tuberculin-specific T-helper-cells lacking the surface receptor CD27, a state associated with advanced differentiation, varied considerably between individuals (from less than 5% to more than 95%). Healthy BCG vaccinated individuals had significantly fewer CD27-negative tuberculin-reactive CD4 T-cells than patients with smear and/or culture positive pulmonary tuberculosis, discriminating these groups with high sensitivity and specificity, whereas individuals with latent tuberculosis infection exhibited levels in between. CONCLUSIONS/SIGNIFICANCE: Smear and/or culture positive pulmonary tuberculosis can be diagnosed by a rapid and reliable immunological test based on the distribution of CD27 expression on peripheral blood tuberculin specific T-cells. This test works very well even in a BCG vaccinated population. It is simple and will be of great utility in situations where sputum specimens are difficult to obtain or sputum-smear is negative. It will also help avoid unnecessary hospitalization and patient isolation

Biogenic opal estimation of deep-sea sediment cores from the Scotia Sea

We present biogenic opal flux records from two deep-sea sites in the Scotia Sea (MD07-3133 and MD07-3134) at decadal-scale resolution, covering the last glacial cycle. Besides conventional and time-consuming biogenic opal measuring methods, we introduce new biogenic opal estimation methods derived from sediment colour b*, wet bulk density, Si/Ti-count ratio, and Fourier transform infrared spectroscopy (FTIRS). All methods capture the biogenic opal amplitude, however, FTIRS - a novel method for marine sediment - yields the most reliable results. 230Th normalization data show strong differences in sediment focusing with intensified sediment focusing during glacial times. At MD07-3134 230Th normalized biogenic opal fluxes vary between 0.2 and 2.5 g/cm2/kyr. Our biogenic opal flux records indicate bioproductivity changes in the Southern Ocean, strongly influenced by sea ice distribution and also summer sea surface temperature changes. South of the Antarctic Polar Front, lowest bioproductivity occurred during the Last Glacial Maximum when upwelling of mid-depth water was reduced and sea ice cover intensified. Around 17 ka, bioproductivity increased abruptly, corresponding to rising atmospheric CO2 contents and decreasing seasonal sea ice coverage

Significantly fewer tuberculin-reactive CD4 T-cells express CD27 in TB-patients than in controls.

<p>Proportions of CD27-positive and negative cells were based on a minimum of 50 IFN-γ positive events. Vertical numbers indicate evaluated events (median and range). Controls included unexposed controls, professionally TB-exposed health care workers, and donors with latent infection. A threshold of 49% would effectively discriminate between patients and controls (dotted line). Controls with latent TB infection had higher values than individuals with no known exposure to TB.</p

Crosstabulation of results in blind study.

<p>Crosstabulation of results in blind study.</p