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Title:   Author  item
                                            Waters, Wadeitem
                                            Nonnecke, Brianitem
                                            FOOTE, M - IOWA STATE UNIVERSITYitem
                                            MAUE, A - UNIVERSITY OF MISSOURIitem
                                            Waters, Theresaitem
                                            Palmer, Mitchellitem
                                            Whipple, Dianaitem
                                            Horst, Ronalditem
                                            ESTES, D - UNIVERSITY OF MISSOURI
  Submitted to: Tuberculosis
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 7/18/2003
                                    Publication  Date: 7/18/2004
                                    Citation: Waters, W.R., Nonnecke, B.J., Foote, M.R., Maue, A.C., Palmer, M.V., Whipple, D.L., Horst, R.L., Estes, D.M. 2004. Mycobacterium bovis bacille calmette guerin vaccination of cattle:  activation of bovine cd4+ and gammadelta tcr+ cells and modulation of 1,25-dihydroxyvitamin d3. Tuberculosis. 83:287-297.Interpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide.  In addition, a recent outbreak of tuberculosis in white-tailed deer in Michigan has seriously hindered eradication efforts within the United States.  Improved techniques are needed for detection of infected cattle.  To develop improved diagnostics, it is beneficial to understand the immune response of cattle to tuberculosis infection.  In this study, specific effects of vitamin D on the immune response of cattle to a live tuberculosis vaccine were determined.  Knowledge obtained from this study will assist in the development of new reagents and methods for the detection of tuberculosis of cattle as well as a better understanding of how cattle respond to tuberculosis vaccines.
                                Technical Abstract: 1,25-dihdroxyvitamin D3 (1,25(OH)2D3) is a potent modulator of immune responses and may be beneficial in the treatment of tuberculosis.  Recent evidence suggest that 1,25(OH)2D3 may affect T-dependent responses in cattle; however, mechanisms by which this vitamin modulates activation of bovine T cells are unclear.  Antigen specific recall responses of Mycobacterium bovis bacille Calmette Guerin (BCG) vaccinated cattle were used as a model system to evaluate effects of 1,25(OH)2D3 on the proliferation and activation of bovine T cell subsets.  CD4+ and gammadelta TCR+ cells were the predominant T cell subsets responding to soluble crude M. bovis-derived antigens (i.e., purified protein derivative and a BCG whole cell sonicate) by proliferation and activation-induced alterations in phenotype.  These subsets exhibited increased CD25 and CD44 mean fluorescence intensity (mfi) and decreased CD62L mfi upon antigen stimulation.  Addition of 1,25(OH)2D3 inhibited proliferation of CD4+ cells and decreased the expression of CD44 on responding (i.e., proliferating) CD4+ and gammadelta TCR+ cells.  These findings suggest that the production of 1,25(OH)2D3 by macrophages within tuberculous lesions would inhibit proliferation and activation of specific lymphocyte subsets and potentially limit tissue damage.


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