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Differential chemokine and cytokine production by neonatal bovine gamma delta T-cell subsets in response to viral toll-like receptor agonists and in vivo respiratory syncytial virus infection

Jodi L McGill
Immunology 2013 v.139 no. pp. 227-244
immunity, agonists, phenotype, T-lymphocytes, Bovine orthopneumovirus, granulocyte-macrophage colony-stimulating factor, transforming growth factor beta, calcitriol, interleukin-10, neonates, receptors, calves, chemokines
Gamma delta T cells respond to stimulation via toll-like receptors (TLR). Bovine gamma delta T cells express TLR3 and TLR7, receptors that are key for the recognition of viruses such as bovine respiratory syncytial virus (BRSV); however, responses of gamma delta T cells to stimulation via these receptors, and their role during viral infections, remains unclear. Here, we demonstrate that neo-natal bovine gamma delta T cells exhibit robust chemokine and cytokine production in response to the TLR3 agonist, Poly(I:C), and the TLR7 agonist, Imiqui-mod. Importantly, we observe a similar phenotype in cd T-cell subsets purified from calves infected with BRSV. Bovine gamma delta T cells are divided into subsets based upon their expression of WC1, and the response to TLR stimulation and viral infection differs between these subsets, with WC1.1+ and WC1neg gamma delta T cells producing macrophage inflammatory pro-tein-1a and granulocyte– macrophage colony-stimulating factor, and WC1.2+ gamma delta T cells preferentially producing the regulatory cytokines inter-leukin-10 and transforming growth factor-b. We further report that the active vitamin D metabolite 1,25-dihydroxyvitamin D3 does not alter cd T-cell responses to TLR agonists or BRSV. To our knowledge, this is the first characterization of the cd T-cell response during in vivo BRSV infec-tion and the first suggestion that WC1.1+ and WC1neg gamma delta T cells contrib-ute to the recruitment of inflammatory populations during viral infection. Based on our results, we propose that circulating gamma delta T cells are poised to rapidly respond to viral infection and suggest an important role for gamma delta T cells in the innate immune response of the bovine neonate.