Free access
Vet. Res.
Volume 41, Number 2, March–April 2010
Number of page(s) 12
Published online 20 October 2009
How to cite this article Vet. Res. (2010) 41:14
How to cite this article: Vet. Res. (2010) 41:14
DOI: 10.1051/vetres/2009062

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

Michael Coad, Derek Clifford, Shelley G. Rhodes, R. Glyn Hewinson, H. Martin Vordermeier and Adam O. Whelan

TB Research Group, Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom

Received 12 August 2009; accepted 16 October 2009; published online 20 October 2009

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-1$\beta$ (IL-1$\beta$) 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-1$\beta$ and elevated IL-10 responses, but importantly, does not influence antigen specific IFN-$\gamma$ responses.

Key words: bovine tuberculosis / skin-testing / gamma-interferon / interleukin-10 / interleukin-1$\beta$

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© INRA, EDP Sciences 2009