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Title:   Author  item
                                            McGill, Jodiitem
                                            Sacco, Randyitem
                                            BALDWIN, CYNTHIA - University Of Massachusettsitem
                                            TELFER, JANICE - University Of Massachusettsitem
                                            Palmer, Mitchellitem
                                            Waters, Wade
  Submitted to: Journal of Immunology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 1/14/2014
                                    Publication  Date: 3/1/2014
                                    Publication URL: http://handle.nal.usda.gov/10113/61552Citation: McGill, J.L., Sacco, R.E., Baldwin, C.L., Telfer, J.C., Palmer, M.V., Waters, W.R. 2014. Specific recognition of mycobacterial protein and peptide antigens by gamma-delta T cell subsets following infection with virulent Mycobacterium bovis. Journal of Immunology. 192(6):2756-2769. doi.org/10.4049/jimmunol.1302567.Interpretive Summary: Bovine tuberculosis causes considerable economic hardship to the livestock industry and represents a significant public health threat worldwide.  Cattle have several subsets of T cells, one being gamma delta T cells.  The different role of these T cell subsets in the immune response to Mycobacterium bovis, the causative agent of bovine tuberculosis, is unknown.  Bovine gamma delta T cell subsets were purified from animals infected with M. bovis and analyzed for their ability to respond to mycobacterial products.  The T cells responded to M. bovis infection, and there was a difference in the role of individual subsets in this immune response.  This is the first demonstration of a unique role for individual gamma delta T cell subsets in the response against bovine tuberculosis.  Additional research is needed to understand the role of individual T cell subsets in the bovine.
                                Technical Abstract: Promoting effective immunity to Mycobacterium bovis infection is a challenge that is of interest to the fields of human and animal medicine alike. We report that 'd T cells from virulent M. bovis infected cattle respond specifically and directly to complex, protein and non-protein mycobacterial antigens.  Importantly, we demonstrate for the first time that bovine 'd T cells specifically recognize small peptide antigens derived from the mycobacterial protein complex early secreted antigenic target 6 kDa protein:10 kDa culture filtrate protein (ESAT6:CFP10) and that this recognition requires direct contact with APC, but is independent of MHC class II.  Furthermore, we show that M. bovis infection in cattle induces robust IL-17A protein responses.  Interestingly, in contrast to results from mice, bovine CD4 T cells and not 'd T cells, are the primary source of this critical pro-inflammatory mediator.  Bovine 'd T cells are divided into subsets based upon their expression of Workshop Cluster 1 (WC1).  We demonstrate that the M. bovis-specific 'd T cell response is composed of a heterogeneous mix of WC1-expressing populations, with WC1.1+ and WC1.2+ subsets responding in vitro to mycobacterial antigens, and both subsets accumulating in the lesions of M. bovis infected animals.  The results described herein enhance our understanding of 'd T cell biology and, as virulent M. bovis infection of cattle represents an excellent model of tuberculosis in humans, contribute to our overall understanding of the role of 'd T cells in the mycobacterial-specific immune response.


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