Repeat tuberculin skin testing leads to desensitisation in naturally infected tuberculous cattle which is associated with elevated interleukin-10 and decreased interleukin-1 beta responses

TB Research Group, Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom.
Veterinary Research (Impact Factor: 3.38). 10/2009; 41(2):14. DOI: 10.1051/vetres/2009062
Source: PubMed

ABSTRACT The principal surveillance tool used to control bovine tuberculosis in cattle is the removal of animals that provide a positive response to the tuberculin skin-test. In this study we performed a longitudinal investigation of the immunological and diagnostic consequences of repeated short-interval skin-tests in cattle naturally infected with Mycobacterium bovis. Tuberculin skin-test positive cattle were subjected to up to four further intradermal comparative cervical skin-tests at approximately 60-day intervals. A significant progressive reduction in the strength of the skin-test was observed after successive tests. In contrast, the magnitude of interferon-gamma (IFN-gamma) responses was not influenced by repeat skin-testing either transiently around the time of each skin-test or longitudinally following repeated tests. A significant boost in blood interleukin-10 (IL-10) production was observed within 3 days following each skin-test although the magnitude of this boosted response returned to lower levels by day 10 post-test. The application of a novel multiplex assay to simultaneously measure seven cytokines and chemokines also identified that skin-testing resulted in a significant and progressive reduction in antigen specific interleukin-1beta (IL-1beta) whilst confirming stable IFN-gamma and elevated IL-10 responses in the blood. Therefore, we have demonstrated that in cattle naturally infected with M. bovis, repeat short-interval skin-testing can lead to a progressive reduction in skin-test responsiveness which has potential negative consequences for the detection of infected animals with marginal or inconclusive skin-test responses. The desensitising effect is associated with decreased IL-1beta and elevated IL-10 responses, but importantly, does not influence antigen specific IFN-gamma responses.

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Available from: Derek Clifford, Aug 20, 2015
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    • "We assessed the effect of pathogen genotype on skin test response (PPD-B – PPD-A) by comparing the influence of genotype with other potential sources of variation, extracting skin test results for animals that tested positive under the standard interpretation . We excluded animals that had an inconclusive result at the previous skin test because they might have become desensitised to tuberculin, characterised by a progressive decrease in response to each subsequent test by cattle undergoing repeated short interval testing (Coad et al., 2009) or those with advanced disease (de la Rua-Domenech et al., 2006). Following these exclusions , 11,799 animals remained, 78% of which were female. "
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    • "To evaluate the presence of IFNc, IL-4 and IL-10 in culture supernatants, the Meso-Scale Discovery (MSD) technology (Gaithersburg , MD, USA) was used as previously described (Coad et al., 2010). Custom coated 7-plex 96-well plates were supplied by MSD. "
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