Mycobacterium bovis bacille Calmette–Guerin vaccination of cattle: activation of bovine CD4 + and γδ TCR + cells and modulation by 1,25-dihydroxyvitamin D 3

Setting : 1,25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ) is a potent modulator of immune responses and may be beneficial in the treatment of tuberculosis. Recent evidence suggest that 1,25(OH) 2 D 3 may affect T-dependent responses in cattle; however, mechanisms by which this vitamin modulates activation of bovine T cells are unclear. Objective : Determine the effects of 1,25(OH) 2 D 3 on the expression of CD25, CD44, and CD62L by bovine T cell subsets proliferating in response to antigen stimulation. Design : 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) 2 D 3 on the proliferation and activation of bovine T cell subsets. Results : CD4 + and γδ 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) 2 D 3 inhibited proliferation of CD4 + cells and decreased the expression of CD44 on responding (i.e., proliferating) CD4 + and γδ TCR + cells. Conclusion : These findings suggest that the production of 1,25(OH) 2 D 3 by macrophages within tuberculous lesions would inhibit proliferation and CD44 expression by co-localized CD4 + and γδ TCR + cells.