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1,25-Dihydroxyvitamin D₃ and Development of Tuberculosis in Cattle

TB Research Group,¹ TSE Molecular Biology Group, Veterinary Laboratories Agency, Addlestone, Surrey KT15 3NB,² Institute for Animal Health, Compton, Berkshire RG20 7NN, United Kingdom³

Received 2 April 2003/ Returned for modification 23 May 2003/ Accepted 23 July 2003

This report describes the presence and activity of 1,25-dihydroxyvitamin D₃ (1,25-D₃) in experimental bovine tuberculosis. Animals that went on to develop tuberculous lesions exhibited a rapid transient increase in serum 1,25-D₃ within the first 2 weeks following infection with Mycobacterium bovis. 1,25-D₃-positive mononuclear cells were later identified in all tuberculous granulomas by immunohistochemical staining of postmortem lymph node tissue. These results suggest a role for 1,25-D₃ both at the onset of infection and in the development of the granuloma in these infected animals. Using a monoclonal antibody to the vitamin D receptor (VDR) as a VDR agonist, we confirmed that activation of the vitamin D pathway profoundly depresses antigen-specific, but not mitogenic, bovine peripheral blood T-cell responses (proliferation and gamma interferon production). Investigation of the mechanism of this suppression showed that the VDR antibody modified the expression of CD80 by accessory cells, such that a significant positive correlation between T-cell proliferation and accessory cell CD80 emerged.

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